ADJUNCTION AND INVERSION OF ADJUNCTION

We establish adjunction and inversion of adjunction for log canonical centers of arbitrary codimension in full generality

An Early Detection of Decline in Rotavirus Cases during the 2013/2014 Season in Japan as Revealed by Time-series Analysis of National Surveillance Data

Rotavirus is a leading cause of severe acute gastroenteritis in children worldwide, and globally licensed vaccines are available. To expedite the introduction of rotavirus vaccines in the national immunisation programme, a simple, ecological method to monitor changes in the burden of rotavirus disease may be of great help. Here, we report an application of a time-series analysis on a publicly-available dataset in Japan on the weekly number of laboratory-confirmed rotavirus-positive samples over the last 5 year period between the 36th week of 2009 and the 35th week of 2014 during which rotavirus vaccines became marketed in Japan and presumed to reach an uptake rate of at least 39% as a national average. Compared with the expected number of rotavirus detection based on the preceding four rotavirus seasons, the number of rotavirus detection during the 2013?2014 season was 42.9% (95% CI: 38.6, 47.8). This suggests that the use of rotavirus vaccine had a positive impact on reducing the burden of rotavirus diarrhoea in Japan. This method, because of its simplicity and little cost, should be applicable to early detection of the impact of rotavirus vaccine even in resource-poor countries where the World Health Organization funded and implemented the sentinel surveillance programmes of laboratory-confirmed rotavirus cases

Administration of an Antioxidant Prevents Lymphoma Development in Transmitochondrial Mice Overproducing Reactive Oxygen Species

Because of the difficulty to exclude possible involvement of nuclear DNA mutations, it has been a controversial issue whether pathogenic mutations in mitochondrial DNA (mtDNA) and the resultant respiration defects are involved in tumor development. To address this issue, our previous study generated transmitochondrial mice (mito-mice-ND613997), which possess the nuclear and mtDNA backgrounds derived from C57BL/6J (B6) strain mice except that they carry B6 mtDNA with a G13997A mutation in the mt-Nd6 gene. Because aged mito-mice-ND613997 simultaneously showed overproduction of reactive oxygen species (ROS) in bone marrow cells and high frequency of lymphoma development, current study examined the effects of administrating a ROS scavenger on the frequency of lymphoma development. We used N-acetylcysteine (NAC) as a ROS scavenger, and showed that NAC administration prevented lymphoma development. Moreover, its administration induced longevity in mito-mice-ND613997. The gene expression profiles in bone marrow cells indicated the upregulation of the Fasl gene, which can be suppressed by NAC administration. Given that natural-killer (NK) cells mediate the apoptosis of various tumor cells via enhanced expression of genes encoding apoptotic ligands including Fasl gene, its overexpression would reflect the frequent lymphoma development in bone marrow cells. These observations suggest that continuous administration of an antioxidant would be an effective therapeutics to prevent lymphoma development enhanced by ROS overproduction

Anaemia, iron deficiency and vitamin A status among school-aged children in rural Kazakhstan.

OBJECTIVES: To investigate the prevalence of anaemia and iron deficiency and vitamin A status among school-aged children in rural Kazakhstan and identify factors associated with anaemia in this population. DESIGN: A cross-sectional design. SETTING: School-aged children in rural Kazakhstan. SUBJECTS: Socio-economic and anthropometric information was collected from 159 school-aged children living in the Kzyl-Orda region of Kazakhstan. Blood samples were collected and the concentrations of haemoglobin (Hb), serum iron, serum ferritin (SF), erythrocyte protoporphyrin (EP), serum retinol and beta-carotene, total iron binding capacity (TIBC), transferrin saturation (TS) and other haematological indices were measured. RESULTS: Among the 159 children, the prevalence of anaemia and iron deficiency defined by the multiple criteria model (SF, TS and EP) was 27% and 13%, respectively. Nine per cent had iron-deficiency anaemia and 21% had serum retinol value < 1.05 micromol l(-1). Mean SF and serum iron concentrations and TS were significantly lower in anaemic children than in their non-anaemic peers, while TIBC and EP were significantly higher in children with anaemia. Hb was significantly correlated with serum iron and retinol concentrations. Serum retinol and SF concentrations and mean corpuscular volume were significantly correlated with Hb by multiple regression analysis. CONCLUSIONS: Anaemia among school-aged children in rural Kazakhstan appears to be related to iron indices and vitamin A status

Mice deficient in the Shmt2 gene have mitochondrial respiration defects and are embryonic lethal

Accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been proposed to be responsible for human aging and age-associated mitochondrial respiration defects. However, our previous findings suggested an alternative hypothesis of human aging—that epigenetic changes but not mutations regulate age-associated mitochondrial respiration defects, and that epigenetic downregulation of nuclear-coded genes responsible for mitochondrial translation [e.g., glycine C-acetyltransferase (GCAT), serine hydroxymethyltransferase 2 (SHMT2)] is related to age-associated respiration defects. To examine our hypothesis, here we generated mice deficient in Gcat or Shmt2 and investigated whether they have respiration defects and premature aging phenotypes. Gcat-deficient mice showed no macroscopic abnormalities including premature aging phenotypes for up to 9 months after birth. In contrast, Shmt2-deficient mice showed embryonic lethality after 13.5 days post coitum (dpc), and fibroblasts obtained from 12.5-dpc Shmt2-deficient embryos had respiration defects and retardation of cell growth. Because Shmt2 substantially controls production of N-formylmethionine-tRNA (fMet-tRNA) in mitochondria, its suppression would reduce mitochondrial translation, resulting in expression of the respiration defects in fibroblasts from Shmt2-deficient embryos. These findings support our hypothesis that age-associated respiration defects in fibroblasts of elderly humans are caused not by mtDNA mutations but by epigenetic regulation of nuclear genes including SHMT2

Specific mitochondrial DNA mutation in mice regulates diabetes and lymphoma development

It has been hypothesized that respiration defects caused by accumulation of pathogenic mitochondrial DNA (mtDNA) mutations and the resultant overproduction of reactive oxygen species (ROS) or lactates are responsible for aging and age-associated disorders, including diabetes and tumor development. However, there is no direct evidence to prove the involvement of mtDNA mutations in these processes, because it is difficult to exclude the possible involvement of nuclear DNA mutations. Our previous studies resolved this issue by using an mtDNA exchange technology and showed that a G13997A mtDNA mutation found in mouse tumor cells induces metastasis via ROS overproduction. Here, using transmitochondrial mice (mito-mice), which we had generated previously by introducing G13997A mtDNA from mouse tumor cells into mouse embryonic stem cells, we provide convincing evidence supporting part of the abovementioned hypothesis by showing that G13997A mtDNA regulates diabetes development, lymphoma formation, and metastasis—but not aging—in this model

Existence of log canonical modifications and its applications

The main purpose of this paper is to establish some useful partial resolutions of singularities for pairs from the minimal model theoretic viewpoint. We first establish the existence of log canonical modifications of normal pairs under some suitable assumptions. Then we recover Kawakita’s inversion of adjunction on log canonicity in full generality. We also discuss the existence of semi-log canonical modifications for demi-normal pairs and construct dlt blow-ups with several extra good properties. As an application, we study lengths of extremal rational curves