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

Clinical Features of Autoimmune Autonomic Ganglionopathy and the Detection of Subunit-Specific Autoantibodies to the Ganglionic Acetylcholine Receptor in Japanese Patients

Autoimmune autonomic ganglionopathy (AAG) is a rare acquired channelopathy that is characterized by pandysautonomia, in which autoantibodies to ganglionic nicotinic acetylcholine receptors (gAChR) may play a central role. Radioimmunoprecipitation (RIP) assays have been used for the sensitive detection of autoantibodies to gAChR in the serum of patients with AAG. Here, we developed luciferase immunoprecipitation systems (LIPS) to diagnose AAG based on IgGs to both the α3 and β4 gAChR subunits in patient serum. We reviewed the serological and clinical data of 50 Japanese patients who were diagnosed with AAG. With the LIPS testing, we detected anti-α3 and -β4 gAChR antibodies in 48% (24/50) of the patients. A gradual mode of onset was more common in the seropositive group than in the seronegative group. Patients with AAG frequently have orthostatic hypotension and upper and lower gastrointestinal tract symptoms, with or without anti-gAChR. The occurrence of autonomic symptoms was not significantly different between the seropositive and seronegative group, with the exception of achalasia in three patients from the seropositive group. In addition, we found a significant overrepresentation of autoimmune diseases in the seropositive group and endocrinological abnormalities as an occasional complication of AAG. Our results demonstrated that the LIPS assay was a useful novel tool for detecting autoantibodies against gAChR in patients with AAG

Repurposable Drugs for Immunotherapy and Strategies to Find Candidate Drugs

Conventional drug discovery involves significant steps, time, and expenses; therefore, novel methods for drug discovery remain unmet, particularly for patients with intractable diseases. For this purpose, the drug repurposing method has been recently used to search for new therapeutic agents. Repurposed drugs are mostly previously approved drugs, which were carefully tested for their efficacy for other diseases and had their safety for the human body confirmed following careful pre-clinical trials, clinical trials, and post-marketing surveillance. Therefore, using these approved drugs for other diseases that cannot be treated using conventional therapeutic methods could save time and economic costs for testing their clinical applicability. In this review, we have summarized the methods for identifying repurposable drugs focusing on immunotherapy

音センサーでピンポン玉の反発係数を測定する

金沢大学附属高等学校タブレット端末の音センサーでピンポン玉の反発係数を測定した結果を紹介する。この方法は従来の距離を測定する方法よりも簡易であること，距離の測定が最初の1回で済むこと，などの利点がある。体育館などでのボールの反発係数を見積もるのに役立つ可能性がある

免疫調節作用を有する新規化合物は亜全身照射による腸死を防ぐA novel immunomodulatory compound that prevents sub-total body irradiation-induced intestinal death

We have found that novel radioprotective agents, which are tentatively designated as compounds A and STA because a patent application is being considered, have remarkable protective effect against intestinal death in mouse sub-total body irradiation (SBI) experiments. In this study, we evaluated the radioprotective activity of a more effective compound, STA, in which one of the core structures of compound A is substituted to an ethyl group in order to enhance blood persistence and enhance the radioprotective effect. As a result, a potent radioprotective effect against radiation enteritis was observed in C57BL/6N mice treated with 26 Gy-SBI. The optimal dose of STA for the radiation protection was 10 mg/kg, while the maximum tolerated dose (MTD) is 40 mg/kg or less in a MTD study. Next, mRNA-Seq analysis of small intestinal mucosa was performed to identify genes related to radiation protection of acute gastrointestinal syndrome by STA. As a result, we found no significant change in any p53 target genes investigated and various changes of autoimmune or inflammatory response-related genes. Especially, many of the Toll-like receptor genes were down-regulated. In addition, SBI experiments were performed on Casp1/4(11)-deficient mice, which show a lack of producing inflammatory cytokines. STA did not show any radioprotective effect on the mice, indicating that the radioprotective effect of STA is dependent on Caspase-1/Caspase-4(11). Currently, we are confirming the reproducibility of the gene expression changes by STA using qPCR, and plan to report the results obtained.日本放射線影響学会第64回大