De Novo Mutations in the Beta-Tubulin Gene TUBB2A Cause Simplified Gyral Patterning and Infantile-Onset Epilepsy

Tubulins, and microtubule polymers into which they incorporate, play critical mechanical roles in neuronal function during cell proliferation, neuronal migration, and postmigrational development: the three major overlapping events of mammalian cerebral cortex development. A number of neuronally expressed tubulin genes are associated with a spectrum of disorders affecting cerebral cortex formation. Such “tubulinopathies” include lissencephaly/pachygyria, polymicrogyria-like malformations, and simplified gyral patterns, in addition to characteristic extracortical features, such as corpus callosal, basal ganglia, and cerebellar abnormalities. Epilepsy is a common finding in these related disorders. Here we describe two unrelated individuals with infantile-onset epilepsy and abnormalities of brain morphology, harboring de novo variants that affect adjacent amino acids in a beta-tubulin gene TUBB2A. Located in a highly conserved loop, we demonstrate impaired tubulin and microtubule function resulting from each variant in vitro and by using in silico predictive modeling. We propose that the affected functional loop directly associates with the alpha-tubulin-bound guanosine triphosphate (GTP) molecule, impairing the intradimer interface and correct formation of the alpha/beta-tubulin heterodimer. This study associates mutations in TUBB2A with the spectrum of “tubulinopathy” phenotypes. As a consequence, genetic variations affecting all beta-tubulin genes expressed at high levels in the brain (TUBB2B, TUBB3, TUBB, TUBB4A, and TUBB2A) have been linked with malformations of cortical development.     

Potential of biosynthesized zinc oxide nanoparticles to control Fusarium wilt disease in eggplant (Solanum melongena) and promote plant growth

BioMetals - In this study, a novel, non-toxic, eco-friendly zinc oxide nanoparticles (ZnO-NPs) was used instead of the synthetic fungicides widely used to control the destructive phytopathogenic...     

Sepsis triggered oxidative stress-inflammatory axis: the pathobiology of reprogramming in the normal sleep–wake cycle

Molecular and Cellular Biochemistry - In individuals with sepsis-related neurodegenerative illness, sleep and circadian rhythm disturbance are common. The alteration in genomic expression linked...     

Protective effect of Echinops galalensis against CCl4-induced injury on the human hepatoma cell line (Huh7)

Phytochemical investigation of the flowering aerial parts of Echinops galalensis (Asteraceae) led to the isolation of a new taraxasteryl triterpene, 3β-acetoxy-taraxast-12, 20(30)-diene-11α-21α-diol (1), together with nine known metabolites, α-amyrin (2), β-sitosterol (3), erythrodiol (4), lup-20(29)-ene-1,3-diol (5), 1,5-dicaffeoylquinic acid (6), 3,5-dicaffeoylquinic acid (7), 3,4-dicaffeoylquinic acid (8), 4,5-dicaffeoylquinic acid (9) and apigenin-7-O-β-d-glucoside (10). The structure of the new compound was determined by comprehensive analyses of their 1D and 2D NMR, mass spectral (HR-EI) data and comparison with previously known analogs. The effect of the methanol extract of E. galalensis, its fractions as well as compounds (1–10) on human hepatoma cell line (Huh7) was evaluated according to aspartate aminotransferase (AST), alanine transaminase (ALT), superoxide dismutase (SOD) activities and malondialdehyde (MDA) level before and after exposure of the cells to carbon tetrachloride (CCl₄). It was found that pre-treatment of human hepatoma cell line (Huh7) with the tested samples (100 μg/ml) prior to CCl₄ challenge protected against cell injury. The protective effect of E. galalensis was suggested to be mediated, at least partly, by its antioxidant activity.     

Tumor localization of newly developed hematoporphyrin (DHP) using a bladder tumor model: a novel hematoporphyrin derivative

Application of laser irradiation with porphyrin(s) or their derivatives for the destruction of tumors in humans requires preliminary studies of their localization in normal and malignant tissues. A novel derivative of hematoporphyrin (HP) was prepared. The newly developed hematoporphyrin (DHP) was administered to Fisher rats with bladder tumors and showed greater accumulation in the tumoral tissues. Comparative data on (HP) and (DHP) are presented and discussed in light of the enhanced tumor porphyrin uptake caused by these agents. The homogeneous intense fluorescence noted with DHP-treated animals suggests that total tumor kill curative therapy will be more feasible. The study paves the way to refining increased porphyrin augment phototherapy and laser application in the field of oncology.