The cell adhesion molecule neuroplastin (Np) is a novel candidate to influence human intelligence. Np-deficient mice display complex cognitive deficits and reduced levels of Plasma Membrane Ca²⁺ ATPases (PMCAs), an essential regulator of the intracellular Ca²⁺ concentration ([iCa²⁺]) and neuronal activity. We show abundant expression and conserved cellular and molecular features of Np in glutamatergic neurons in human hippocampal-cortical pathways as characterized for the rodent brain. In Nptn ^{lox/loxEmx1Cre} mice, glutamatergic neuron-selective Np ablation resulted in behavioral deficits indicating hippocampal, striatal, and sensorimotor dysfunction paralleled by highly altered activities in hippocampal CA1 area, sensorimotor cortex layers I-III/IV, and the striatal sensorimotor domain detected by single-photon emission computed tomography. Altered hippocampal and cortical activities correlated with reduction of distinct PMCA paralogs in Nptn ^{lox/loxEmx1Cre} mice and increased [iCa²⁺] in cultured mutant neurons. Human and rodent Np enhanced the post-transcriptional expression of and co-localized with PMCA paralogs in the plasma membrane of transfected cells. Our results indicate Np as essential for PMCA expression in glutamatergic neurons allowing proper [iCa²⁺] regulation and normal circuit activity. Neuron-type-specific Np ablation empowers the investigation of circuit-coded learning and memory and identification of causal mechanisms leading to cognitive deterioration.

Background/Objectives: Strabismus is the most common ocular disorder of childhood. Three rare, recurrent genetic duplications have been associated with both esotropia and exotropia, but the mechanisms by which they contribute to strabismus are unknown. This work aims to investigate the mechanisms of the smallest of the three, a 23 kb duplication on chromosome 4 (hg38|4:25,554,985-25,578,843). Methods: Using CRISPR and bridging oligos, we introduced the duplication into the Kolf2.1J iPSC line. We differentiated the parent line and the line with the duplication into cortical neurons using a three-dimensional differentiation protocol, and performed bulk RNASeq on neural progenitors (day 14) and differentiated neurons (day 63). Results: We successfully introduced the duplication into Kolf2.1J iPSCs by nucleofecting a bridging oligo for the newly formed junction along with cas9 ribonucleoparticles. We confirmed that the cells had a tandem duplication without inversion or deletion. The parent line and the line with the duplication both differentiated into neurons reliably. There were a total of 37 differentially expressed genes (DEGs) at day 63, 25 downregulated and 12 upregulated. There were 55 DEGs at day 14, 18 of which were also DEGs at day 63. The DEGs included a number of protocadherins, several genes involved in neuronal development, including SLITRK2, CSMD1, and VGF, and several genes of unknown function. Conclusions: A copy number variant (CNV) that confers risk for strabismus affects gene expression of several genes involved in neural development, highlighting that strabismus most likely results from abnormal neural development, and identifying several new genes and pathways for further research into the pathophysiology of strabismus.

Context: Amlapitta Mishran suspension is a poly herbal ayurvedic formulation, which has been traditionally used for acidity and gastric ulcers. Aim: The aim of this study is to evaluate the antiulcer activity of Amlapitta Mishran on non-steroidal anti-inflammatory drugs (NSAID's) -induced ulcers in the rat model. Subjects and Methods: The antiulcer activity of Amlapitta Mishran was investigated on indomethacin (100 mg/kg) NSAID's induced ulcers in rats. Effect of two different doses of Amlapitta Mishran was studied by calculating the total number of ulcers, ulcer index and percentage inhibition. Statistical Analysis Used: Data was analyzed by the Student's t-test (P < 0.05). Results: Amlapitta Mishran treated rats have shown significant (P < 0.0001) decrease in the total number of ulcers and ulcer index and significant increase in % inhibition of ulcers as compared with positive control group. Conclusion: The results indicate that Amlapitta Mishran has showed a dose dependent antiulcer activity in experimental animals and confirms ayurvedic use of Amlapitta Mishran in gastric ulcers.