Induction of liver-resident memory T cells and protection at liver-stage malaria by mRNA-containing lipid nanoparticles.

Recent studies have suggested that CD8+ liver-resident memory T (TRM) cells are crucial in the protection against liver-stage malaria. We used liver-directed mRNA-containing lipid nanoparticles (mRNA-LNPs) to induce liver TRM cells in a murine model. Single-dose intravenous injections of ovalbumin mRNA-LNPs effectively induced antigen-specific cytotoxic T lymphocytes in a dose-dependent manner in the liver on day 7. TRM cells (CD8+ CD44hi CD62Llo CD69+ KLRG1-) were induced 5 weeks after immunization. To examine the protective efficacy, mice were intramuscularly immunized with two doses of circumsporozoite protein mRNA-LNPs at 3-week intervals and challenged with sporozoites of Plasmodium berghei ANKA. Sterile immunity was observed in some of the mice, and the other mice showed a delay in blood-stage development when compared with the control mice. mRNA-LNPs therefore induce memory CD8+ T cells that can protect against sporozoites during liver-stage malaria and may provide a basis for vaccines against the disease.

Generation of a human induced pluripotent stem cell line, BRCi009-A, derived from a patient with glycogen storage disease type 1a.

Glycogen storage disease type 1a (GSD1a) is an autosomal recessive disorder caused by mutations of the glucose-6-phosphatase (G6PC) gene. Mutations of the G6PC gene lead to excessive accumulation of glycogen in the liver, kidney, and intestinal mucosa due to the deficiency of microsomal glucose-6-phosphatase. Human induced pluripotent stem cells (iPSCs) enable the production of patient-derived hepatocytes in culture and are therefore a promising tool for modeling GSD1a. Here, we report the establishment of human iPSCs from a GSD1a patient carrying a G6PC mutation (c.648G > T; p.Leu216 = ).

Spatial distribution and temporal variation of Microcystis species composition and microcystin concentration in Lake Biwa.

Spatial and temporal variation in Microcystis species composition and microcystin concentration, quantified by enzyme-linked immunosorbent assay and high-performance liquid chromatography, were investigated during a 3-year period (1998-2000) in the Northern Basin of Lake Biwa. The Northern Basin generally had a concentration of 5 microg L(-1) or less, except at station 1 (Nagahama Bay) from July to October during the study period. The maximum concentration at station 1 was 22.7, 35.9, and 22.0 microg L(-1) in October of 1998, 1999, and 2000, respectively. Eleven species of cyanobacteria were observed: Microcystis aeruginosa, M. ichthyoblabe, M. novacekii, M. wesenbergii, Oscillatoria raciborskii, Anabaena oumiana, A. affinis, A. flos-aquae, A. ucrainica, A. smithii, and A. crassa. Of these, M. aeruginosa and M. wesenbergii were the main components observed. A high concentration of microcystin in the lake water was mostly a result of variation in the relative amount of toxic M. aeruginosa rather than of the total Microcystis cell number. This was supported by the analytical results for isolated strains. Microcystis spp. cell density in the Northern Basin appeared to increase gradually over the course of the study. This is the first study to have surveyed the Northern Basin of Lake Biwa, which supplies drinking water to 14 million people and is the largest lake in Japan.