Variations in societal characteristics of spatial disease clusters: examples of colon, lung and breast cancer in Japan

BACKGROUND: Spatial analyses and ecological studies are essential for epidemiology and public health. The present study combining these two methods was performed to identify spatial clusters of selected types of cancer in Japan and to determine their societal characteristics focusing on homogeneity among clusters. RESULTS: Spatial clusters of high mortality rates of male colon and lung cancer and of female breast cancer were identified by the spatial scan statistic using Japanese municipal data (N = 3360) from 1993 to 1998 and also municipalities were divided into four societal clusters based on socioeconomic indicators and population density (urban-rich, suburban, rural-poor, and clutter). Five, seven, and four mortality clusters were identified for lung, colon and breast cancer, respectively. For colon and breast cancer, most municipalities of all except one cluster were included in a single societal cluster (urban-rich). The municipalities associated with mortality clusters for lung cancer belonged to various societal clusters. CONCLUSION: Increased mortality rates of colon and breast cancer can be explained by homogenous societal characteristics related to urbanisation, although there were exceptional areas with higher mortality rates. The regional variation in lung cancer mortality rate appeared to be due to heterogeneous factors. These findings and the analysis performed in the present study will contribute to both nationwide and region-specific cancer prevention strategies

The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune Responses

Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces the IFN antiviral response. However, the regulatory mechanisms that mediate cGAS-triggered signaling have not been fully explored. Here, we show the involvement of a small GTPase, RAB2B, and its effector protein, Golgi-associated RAB2B interactor-like 5 (GARIL5), in the cGAS-mediated IFN response. RAB2B-deficiency affects the IFN response induced by cytosolic DNA. Consistent with this, RAB2B deficiency enhances replication of vaccinia virus, a DNA virus. After DNA stimulation, RAB2B colocalizes with stimulator of interferon genes (STING), the downstream signal mediator of cGAS, on the Golgi apparatus. The GTP-binding activity of RAB2B is required for its localization on the Golgi apparatus and for recruitment of GARIL5. GARIL5 deficiency also affects the IFN response induced by cytosolic DNA and enhances replication of vaccinia virus. These findings indicate that the RAB2B-GARIL5 complex promotes IFN responses against DNA viruses by regulating the cGAS-STING signaling axis

Production of doubly strange hypernuclei via {\Xi}- doorways in the 16O(K-, K+) reaction at 1.8 GeV/c

We examine theoretically production of doubly strange hypernuclei, 16 {\Xi}-C and 16 {\Lambda}{\Lambda}C, in doublecharge exchange 16O(K-, K+) reactions using a distorted-wave impulse approximation. The inclusive K+ spectrum at the incident momentum pK- = 1.8 GeV/c and scattering angle {\theta}lab = 0^{\circ} is estimated in a one-step mechanism, K-p \to K+{\Xi}- via {\Xi}- doorways caused by a {\Xi}-p-{\Lambda}{\Lambda} coupling. The calculated spectrum in the {\Xi}- bound region indicates that the integrated cross sections are on the order of 7-12 nb/sr for significant 1- excited states with 14C(0+, 2+) \otimes s{\Lambda}p{\Lambda} configurations in 16 {\Lambda}{\Lambda}C via the doorway states of the spin-stretched 15N(1/2-, 3/2-) \otimes s{\Xi}- in 16 {\Xi}-C due to a high momentum transfer q{\Xi}- \approx 400 MeV/c. The {\Xi}- admixture probabilities of these states are on the order of 5-9%. However, populations of the 0+ ground state with 14C(0+) \otimes s2{\Lambda} and the 2+ excited state with 14C(2+) \otimes s2 {\Lambda} are very small. The sensitivity of the spectrum on the {\Xi}N-{\Lambda}{\Lambda} coupling strength enables us to extract the nature of {\Xi}N-{\Lambda}{\Lambda} dynamics in nuclei, and the nuclear (K-, K+) reaction can extend our knowledge of the S = -2 world.Comment: 10 pages, 3 figure

The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune Responses

Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces the IFN antiviral response. However, the regulatory mechanisms that mediate cGAS-triggered signaling have not been fully explored. Here, we show the involvement of a small GTPase, RAB2B, and its effector protein, Golgi-associated RAB2B interactor-like 5 (GARIL5), in the cGAS-mediated IFN response. RAB2B-deficiency affects the IFN response induced by cytosolic DNA. Consistent with this, RAB2B deficiency enhances replication of vaccinia virus, a DNA virus. After DNA stimulation, RAB2B colocalizes with stimulator of interferon genes (STING), the downstream signal mediator of cGAS, on the Golgi apparatus. The GTP-binding activity of RAB2B is required for its localization on the Golgi apparatus and for recruitment of GARIL5. GARIL5 deficiency also affects the IFN response induced by cytosolic DNA and enhances replication of vaccinia virus. These findings indicate that the RAB2B-GARIL5 complex promotes IFN responses against DNA viruses by regulating the cGAS-STING signaling axis

Curcumin analog, GO-Y078, overcomes resistance to tumor angiogenesis inhibitors

Tumor angiogenesis inhibition is one of the most potent strategies in cancer chemotherapy. From past clinical studies, inhibition of the vascular endothelial growth factor pathway successfully treats malignant tumors. However, vascular endothelial growth factor inhibitors alone cannot cure tumors. Moreover, resistance to small molecule inhibitors has also been reported. Herein, we show the antiangiogenic potential of a newly synthesized curcumin analog, GO-Y078, that possibly functions through inhibition of actin stress fiber formation, resulting in mobility inhibition; this mechanism is different from that of vascular endothelial growth factor inhibition. In addition, we examined the detailed mechanism of action of the antiangiogenesis potential of GO-Y078 using human umbilical venous epithelial cells resistant to angiogenesis inhibitors (HUVEC-R). GO-Y078 inhibited the growth and mobility of HUVEC-R at 0.75mol/L concentration. Expression analyses by microarray and RT-PCR showed that expressions of genes including that of fibronectin 1 were significantly suppressed. Among these genes, fibronectin 1 is abundantly expressed and, therefore, seems to be a good target for GO-Y078. In a knockdown experiment using Si-oligo of fibronectin 1 (FN1), FN1 expression was decreased to half of that in mock experiments as well as GO-Y078. Knockdown of FN1 resulted in the suppression of HUVEC-R growth at 24hours after treatment. Fibronectin is a key molecule contributing to angiogenesis that could be inhibited by GO-Y078. Thus, resistance to vascular endothelial growth factor inhibition can be overcome using GO-Y078

Municipal health expectancy in Japan: decreased healthy longevity of older people in socioeconomically disadvantaged areas

BACKGROUND: Little is known about small-area variation in healthy longevity of older people and its socioeconomic correlates. This study aimed to estimate health expectancy at 65 years (HE65) at the municipal level in Japan, and to examine its relation to area socio-demographic conditions. METHODS: HE65 of municipalities (N = 3361) across Japan was estimated by a linear regression formula with life expectancy at 65 years and the prevalence of those certificated as needing nursing care. The relation between HE65 and area socio-demographic indicators was examined using correlation coefficients. RESULTS: The estimated HE65 (years) ranged from 13.13 to 17.39 for men and from 14.84 to 20.53 for women. HE65 was significantly positively correlated with the proportion of elderly and per capita income, and negatively correlated with the percentage of households of a single elderly person, divorce rate, and unemployment rate. These relations were stronger in large municipalities (with a population of more than 100,000) than in small and medium-size municipalities. CONCLUSION: A decrease in healthy longevity of older people was associated with a higher percentage of households of a single elderly person and divorce rate, and lower socioeconomic conditions. This study suggests that older people in urban areas are susceptible to socio-demographic factors, and a social support network for older people living in socioeconomically disadvantaged conditions should be encouraged