Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

p38 MAP kinase の抑制はマウスの圧負荷による病的心肥大を軽減し心機能低下を抑制する

Background: P38 mitogen-activated protein kinase（MAP kinase）plays on important role for progression of pathological cardiac hypertrophy. However, the role of p38 MAP kinase in cardiac hypertrophy induced by pressure overload remains unclear. We investigated the effect of chronic treatment with p38 MAP kinase inhibitor on the development of heart failure induced by transverse aortic constriction（TAC）in mice. Methods and Results: TAC increased left ventricular septal wall thickness（LVSWT）and cross-sectional area（CSA）of cardiomyocyte, and decreased LV fractional shortening（FS）compared with sham operation after 6 weeks. TAC also increased phosphorylation of p38 MAP kinase, whereas other hypertrophic signals were unchanged. In another experiment, TAC mice and sham operated mice were treated with subcutaneous injection of p38 MAP kinase inhibitor SB202190（5mg/kg/day）or placebo five times a week for six weeks. Treatment with p38 MAP kinase inhibitor attenuated the increase in LVSWT and CSA, and the decrease in FS in mice with TAC. Conclusions: Inhibition of p38 MAP kinase attenuated left ventricular hypertrophy and inhibited progression of systolic dysfunction in pressure overload-induced cardiac hypertrophy. These results suggest that inhibition of p38 MAP kinase has a protective effect for development of heart failure induced by pressure overload

Combined Pre-Supernova Alert System with Kamland and Super-Kamiokande

International audiencePreceding a core-collapse supernova, various processes produce an increasing amount of neutrinos of all flavors characterized by mounting energies from the interior of massive stars. Among them, the electron antineutrinos are potentially detectable by terrestrial neutrino experiments such as KamLAND and Super-Kamiokande via inverse beta decay interactions. Once these pre-supernova neutrinos are observed, an early warning of the upcoming core-collapse supernova can be provided. In light of this, KamLAND and Super-Kamiokande have been monitoring pre-supernova neutrinos since 2015 and 2021, respectively. Recently, we performed a joint study between KamLAND and Super-Kamiokande on pre-supernova neutrino detection. A pre-supernova alert system combining the KamLAND detector and the Super-Kamiokande detector is developed and put into operation, which can provide a supernova alert to the astrophysics community. Fully leveraging the complementary properties of these two detectors, the combined alert is expected to resolve a pre-supernova neutrino signal from a 15 M$_{\odot}$ star within 510 pc of the Earth, at a significance level corresponding to a false alarm rate of no more than 1 per century. For a Betelgeuse-like model with optimistic parameters, it can provide early warnings up to 12 hours in advance