Heterozygous variants in TBCK cause a mild neurologic syndrome in humans and mice.

TBCK-related encephalopathy is a rare pediatric neurodegenerative disorder caused by biallelic loss-of-function variants in the TBCK gene. After receiving anecdotal reports of neurologic phenotypes in both human and mouse TBCK heterozygotes, we quantified if TBCK haploinsufficiency causes a phenotype in mice and humans. Using the tbck+/- mouse model, we performed a battery of behavioral assays and mTOR pathway analysis to investigate potential alterations in neurophysiology. We conducted as well a phenome-wide association study (PheWAS) analysis in a large adult biobank to determine the presence of potential phenotypes associated to this variant. The tbck+/- mouse model demonstrates a reduction of exploratory behavior in animals with significant sex and genotype interactions. The concurrent PheWAS analysis of 10,900 unrelated individuals showed that patients with one copy of a TBCK loss-of-function allele had a significantly higher rate of acquired toe and foot deformities, likely indicative of a mild peripheral neuropathy phenotype. This study presents an example of what may be the underappreciated occurrence of mild neurogenic symptoms in heterozygote individuals of recessive neurogenetic syndromes.

Lectin isolated from Abelmoschus esculentus induces caspase mediated apoptosis in human U87 glioblastoma cell lines and modulates the expression of circadian clock genes.

Lectins are a cluster of proteins which are capable of recognizing and binding to glycoconjugates and are extensively found in plants, animals, fungi and bacteria. Plant-derived lectins have been gaining importance over the years due to their innumerable biological activities and also have the added possibility of being compatible to the human system while simultaneously exhibiting properties like antimicrobial and antitumor activities. Abelmoschus esculentus (AE) commonly known as okra is a vegetable with medicinal properties. AE extracts are used to treat disorders such as constipation, microbial infection, urine retention, hypoglycemia and inflammation in humans. Previous studies showed that lectin isolated from AE exhibited anti inflammatory, anti nociceptive, anticancer, antioxidant and hemagglutinating activities. However, the antitumor effect of the lectin derived from this plant against neural cancer cells still remains unexplored. Glioblastoma is a malignant tumor of the nervous system. Treatment options for patients afflicted by glioblastoma is limited to surgical resection, preceded by radiation therapy and followed by chemotherapy. Hence it would be of interest to identify novel bio molecules with ability to selectively target glioblastoma with minimum side effects. In this aspect, lectins from vegetables that are commonly used as food products could offer a promising lead as anticancer molecules. The present study proves the anti-proliferative effect of lectin isolated from AE on human U87 glioma cells. MTT assay showed significant concentration dependent cytotoxic activity and the IC50 value was calculated as 21 µg/ml. Further, annexin V/FITC staining by FACS, the expression of caspase 3 and 7 and the circadian genes clock and Bmal1 using RT-PCR and the generation of intracellular ROS, cell cycle analysis by FACS revealed the ability of AEL to induce effective apoptosis.