A novel missense mutation in CCDC88C activates the JNK pathway and causes a dominant form of spinocerebellar ataxia.

BACKGROUND: Spinocerebellar ataxias (SCAs) are a group of clinically and genetically diverse and autosomal-dominant disorders characterised by neurological deficits in the cerebellum. At present, there is no cure for SCAs. Of the different distinct subtypes of autosomal-dominant SCAs identified to date, causative genes for only a fraction of them are currently known. In this study, we investigated the cause of an autosomal-dominant SCA phenotype in a family that exhibits cerebellar ataxia and pontocerebellar atrophy along with a global reduction in brain volume. METHODS AND RESULTS: Whole-exome analysis revealed a missense mutation c.G1391A (p.R464H) in the coding region of the coiled-coil domain containing 88C (CCDC88C) gene in all affected individuals. Functional studies showed that the mutant form of CCDC88C activates the c-Jun N-terminal kinase (JNK) pathway, induces caspase 3 cleavage and triggers apoptosis. CONCLUSIONS: This study expands our understanding of the cause of autosomal-dominant SCAs, a group of heterogeneous congenital neurological conditions in humans, and unveils a link between the JNK stress pathway and cerebellar atrophy.

Monitoring bacterial growth using tunable resistive pulse sensing with a pore-based technique.

A novel bacterial growth monitoring method using a tunable resistive pulse sensor (TRPS) system is introduced in this study for accurate and sensitive measurement of cell size and cell concentration simultaneously. Two model bacterial strains, Bacillus subtilis str.168 (BSU168) and Escherichia coli str.DH5α (DH5α), were chosen for benchmarking the growth-monitoring performance of the system. Results showed that the technique of TRPS is sensitive and accurate relative to widely used methods, with a lower detection limit of cell concentration measurement of 5 × 105 cells/ml; at the same time, the mean coefficient of variation from TRPS was within 2 %. The growth of BSU168 and DH5α in liquid cultures was studied by TRPS, optical density (OD), and colony plating. Compared to OD measurement, TRPS-measured concentration correlates better with colony plating (R = 0.85 vs. R = 0.72), which is often regarded as the gold standard of cell concentration determination. General agreement was also observed by comparing TRPS-derived cell volume measurements and those determined from microscopy. We have demonstrated that TRPS is a reliable method for bacterial growth monitoring, where the study of both cell volume and cell concentration are needed to provide further details about the physical aspects of cell dynamics in real time.