Highlights d CHP1 regulates the major route of glycerolipid synthesis in mammals and invertebrates d CHP1 binds and activates GPAT4, the rate-limiting enzyme of ER glycerolipid synthesis d Activation of GPAT4 requires myristoylation of CHP1 d Loss of CHP1-GPAT4 complex leads to a dependency on peroxisomal lipid synthesis

Neurodevelopmental disorders (NDDs) include a broad spectrum of disorders that disrupt normal brain development. Though some NDDs are caused by acquired insults (i.e., toxic or infectious encephalopathy) or may be cryptogenic, many NDDs are caused by variants in a single gene or groups of genes that disrupt neuronal development or function. In this review, we will focus on those NDDs with a genetic etiology. The exact mechanism, timing, and progression of the molecular pathology are seldom well known; however, the abnormalities in development typically manifest in similar patterns such as delays or regression in motor function, social skills, and language or cognitive abilities. Severity of impairment can vary widely. At present, only symptomatic treatments are available to manage seizures and behavioral problems commonly seen in NDDs. In recent years, there has been a rapid expansion of research into gene therapy using adeno-associated viruses (AAVs). Using AAVs as vectors to replace the non- or dysfunctional gene in vivo is a relatively simple model which has created an unprecedented opportunity for the future of NDD treatment. Advances in this field are of paramount importance as NDDs lead to a massive lifelong burden of disease on the affected individuals and families. In this article, we review the unique advantages and challenges of AAV gene therapies. We then look at potential applications of gene therapy for 3 of the more common NDDs (Rett syndrome, fragile X syndrome, and Angelman syndrome), as well as 2 less common NDDs (<i>SLC13A5</i> deficiency disorder and <i>SLC6A1</i>-related disorder). We will review the available natural history of each disease and current state of preclinical studies including a discussion on the application of AAV gene therapies for each disease.

Acidosis is the most dangerous complication of subarachnoid hemorrhage (SAH). Although the carotid bodies (CBs) network is essential for pH regulation, neither binuclear neurons (BNN) nor their functions have been mentioned so far in the literature. The aim of this study was to investigate the crucial roles of mononuclear (MNN) or BNN in CBs on acidosis following SAH. Twenty-five hybrid rabbits were used. Five rabbits were used as a control group, six for sham, and the remaining 14 rabbits were used as the study group by injection of 1 mL of autologous arterial blood into the cisterna magna to produce SAH. Normal and degenerated MNN/BNN densities of CBs were counted by stereological methods. The mean blood pH values were: 7.362 AE 0.041 in the control group; 7.324 AE 0.064 in sham, 7.272 AE 0.062 in the SAH group. The degenerated MNN and BNN values were 5 AE 1/mm 3 and 9 AE 3/mm 3 in the control group; 15 AE 5/ mm 3 and 22 AE 6/mm 3 in sham, 965 AE 113/mm 3 and 1532 AE 176/mm 3 in the SAH group. Mean pH values were under 7.212 AE 0.130 in animals with prominent degenerated BNN. The differences between MNN/pH changes were significant between the SAH and control groups (P < 0.005); whereas BNN/pH values were significant between the SAH and sham groups (pH < 0.005), SAH and control (P < 0.0001). BNN degeneration could result in more severe acidosis than MNN following SAH which has not been described so far.

Fibroblasts from a Familial Mediterranean Fever (FMF) patient were reprogrammed with episomal vectors by using the Neon Transfection System for the generation of integration-free induced pluripotent stem cells (iPSCs). The resulting iPSC line was characterized to determine the expression of pluripotency markers, proper differentiation into three germ layers, the presence of normal chromosomal structures as well as the lack of genomic integration. A homozygous missense mutation in the MEFV gene (p.Met694Val), which lead to typical FMF phenotype, was shown to be present in the generated iPSC line.

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