👤 Tatsuo Ohya

Cellular and subcellular morphology reflects the physiological state of a cell. To determine the physiological nature of sake yeast with superior fermentation properties, we quantitatively analyzed the morphology of sake yeast cells by using the CalMorph system. All the sake strains examined here exhibited common morphological traits that are typically observed in the well-characterized whiskey (whi) mutants that show accelerated G(1)/S transition. In agreement with this finding, the sake strain showed less efficient G(0)/G(1) arrest and elevated expression of the G(1) cyclin gene CLN3 throughout the fermentation period. Furthermore, deletion of CLN3 remarkably impaired the fermentation rate in both sake and laboratory strains. Disruption of the SWI6 gene, a transcriptional coactivator responsible for Cln3p-mediated G(1)/S transition, also resulted in a decreased fermentation rate, whereas whi mutants exhibited significant improvement in the fermentation rate, demonstrating positive roles of Cln3p and its downstream signalling pathway in facilitating ethanol fermentation. The combined results indicate that enhanced induction of CLN3 contributes to the high fermentation rate of sake yeast, which are natural whi mutants. Show less

The juvenile form of neuronal ceroid lipofuscinosis (JNCL) is caused by mutations in the CLN3 gene, and is characterized by progressive loss of vision and development of motor deficits. A few patients exhibit a more protracted clinical course and are diagnosed with protracted JNCL (PJNCL). Here, we report the autopsy in a case of PJNCL in a 55-year-old male and immunohistochemical examination of the involvement of oxidative stress and glutamate excitotoxicity in neurodegeneration. The patient was born to consanguineous parents (I assume this means that the parents were related. If not, then the sentence will need to be changed again.) and had brothers with similar neurological disease. He showed mental retardation and visual impairment in the first decade which gradually developed along with motor dysfunction for over 40 years. At autopsy, the cerebral pyramidal neurons revealed deposition of lipopigments, which demonstrated 'finger print' and curvilinear profiles on electron microscopy. He also exhibited cerebellar cortical atrophy, fibrillary gliosis in the white matter, and rarefication in the globus pallidus. Immunohistochemically, the number of neurons immunoreactive for advanced glycation end product was elevated in the cerebellar cortex and midbrain. Immunoreactivity for excitatory amino acid transporter 1 was reduced in the cerebellar dentate and inferior olivary nuclei. These findings suggest that oxidative damage to proteins and disturbed glutamate transport can be involved in PJNCL. Show less