Role of ferritinophagy in cystine deprivation-induced cell death in glioblastoma cells

Ferroptosis is a form of cell death caused by iron-dependent lipid peroxidation. Cancer cells increase cystine uptake for the synthesis of glutathione (GSH), which is used by glutathione peroxidase 4 to reduce lipid peroxides. Here, we report that cystine deprivation in glioblastoma cells, but not inhibition of GSH synthesis by l-buthionine sulfoximine (BSO), induces ferroptosis. We found that cystine deprivation decreased the protein levels of ferritin heavy chain FTH1, whereas it was increased by BSO treatment. The lysosome inhibitor bafilomycin A1 or deletion of nuclear receptor coactivator 4 (NCOA4) inhibited cystine deprivation-induced decrease in FTH1 protein levels and cell death. In addition, cystine deprivation induced microtubule-associated protein light chain 3 (LC3)-II protein accumulation, suggesting that cystine deprivation induces ferritinophagy. BSO causes cell death when glioblastoma cells are treated with iron inducers, ferrous ammonium sulfate or hemin. On the other hand, cystine deprivation-induced degradation of FTH1 and cell death required glutamine. This study suggests that ferritinophagy, in addition to GSH depletion, plays an important role in cystine deprivation-induced ferroptosis in glioblastoma cells

Dimensional Hierarchy in Quantum Hall Effects on Fuzzy Spheres

We construct higher dimensional quantum Hall systems based on fuzzy spheres. It is shown that fuzzy spheres are realized as spheres in colored monopole backgrounds. The space noncommutativity is related to higher spins which is originated from the internal structure of fuzzy spheres. In $2k$-dimensional quantum Hall systems, Laughlin-like wave function supports fractionally charged excitations, $q=m^{-{1/2}k(k+1)}$ (m is odd). Topological objects are ($2k-2$)-branes whose statistics are determined by the linking number related to the general Hopf map. Higher dimensional quantum Hall systems exhibit a dimensional hierarchy, where lower dimensional branes condense to make higher dimensional incompressible liquid.Comment: 4 pages, 1 figur

Aging of hospital physicians in rural Japan: A longitudinal study based on national census data

Background The disparity in the number of urban and rural physicians is a social problem in Japan. There may also be a disparity in the age of physicians. This study longitudinally examines both geographic and age distributions of physicians. Methods Individual data from the Survey of Physicians, Dentists and Pharmacists in 1994, 2004 and 2014 and municipality data from the National Population Census were used. The 2015 municipality border was applied to all years, and all municipalities were classified into equalsize quintiles based on population density. Both municipalities and physicians were longitudinally observed. Results Between 1994 and 2014, the number of physicians per 100,000 population increased by 31.8% in the most urban group of municipalities and 17.4% in the most rural group. The average age of physicians was highest in the most rural and lowest in the most urban group. The difference in average age between the urban and rural physicians widened from 2.1 years in 1994 to 6.0 years in 2014. This disparity is particularly pronounced among hospital physicians (from 1.5 years in 1994 to 7.6 years in 2014). In the most rural group, the number of hospital physicians younger than 40 years old has decreased by 59.4%, while the number of those 55±70 has grown by 153% and the number older than 70 years old by 41.0%. Between 1994 and 2004, only 23.0% of hospital physicians younger than 40 years old were retained in the most rural group; the retention rate fell to 19.3% between 2004 and 2014, while the rates increased in older physicians. Conclusions The uneven distribution of physicians is increasing in Japan, as is the aging of rural hospital physicians. Shortage of physicians in rural areas may be more serious than that shown as their headcount.This research was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 16K09145 (http://www.jsps.go.jp/english/e-grants/index.html) (KI)

An fMRI Study of Word Reading and Colour Recognition in Different Quadrant Fields

This fMRI study analyzed activations for processing of word and colour, which were presented in each of the four quadrants, to investigate anatomical segregation between colour and orientation processing and also to examine the effect of visual stimulus position on brain activations. Main effect of visual category was found in the bilateral extrastriate cortices extending to the left visual word form area (word > colour) and small area of the right ventrolateral prefrontal cortex (colour > word). ROI analysis showed that there was a tendency that V4α, not V4/8, showed a greater response to colours than to words. Main effect of visual fields was found in early visual areas, which showed greater responses to the left than to the right field stimuli and also to the lower than to the upper field stimuli. No significant interactions between visual category and visual fields were found