Result of Space Particle Monitor (SPM) on-Orbit Demonstration

Space Particle Monitor (SPM) is a compact, lightweight and low-cost radiation measurement device that applies two PIN silicon semiconductor detectors. SPM was developed in the SERVIS (Space Environment Reliability Verification Integrated System) project under the Ministry of Economy, Trade and Industry (METI), and is mounted on JAXA RAPid Innovative payload demonstration Satellite 1 (RAPIS-1) launched in January 2019. We achieved the full success that the discrimination and energy content of electrons, protons, and heavy ions could be observed. This paper reports on-orbit demonstration results of SPM

Important cardiac transcription factor genes are accompanied by bidirectional long non-coding RNAs

BackgroundHeart development is a relatively fragile process in which many transcription factor genes show dose-sensitive characteristics such as haploinsufficiency and lower penetrance. Despite efforts to unravel the genetic mechanism for overcoming the fragility under normal conditions, our understanding still remains in its infancy. Recent studies on the regulatory mechanisms governing gene expression in mammals have revealed that long non-coding RNAs (lncRNAs) are important modulators at the transcriptional and translational levels. Based on the hypothesis that lncRNAs also play important roles in mouse heart development, we attempted to comprehensively identify lncRNAs by comparing the embryonic and adult mouse heart and brain.ResultsWe have identified spliced lncRNAs that are expressed during development and found that lncRNAs that are expressed in the heart but not in the brain are located close to genes that are important for heart development. Furthermore, we found that many important cardiac transcription factor genes are located in close proximity to lncRNAs. Importantly, many of the lncRNAs are divergently transcribed from the promoter of these genes. Since the lncRNA divergently transcribed from Tbx5 is highly evolutionarily conserved, we focused on and analyzed the transcript. We found that this lncRNA exhibits a different expression pattern than that of Tbx5, and knockdown of this lncRNA leads to embryonic lethality.ConclusionThese results suggest that spliced lncRNAs, particularly bidirectional lncRNAs, are essential regulators of mouse heart development, potentially through the regulation of neighboring transcription factor genes

Disruption of entire Cables2 locus leads to embryonic lethality by diminished Rps21 gene expression and enhanced p53 pathway

In vivo function of CDK5 and Abl enzyme substrate 2 (Cables2), belonging to the Cables protein family, is unknown. Here, we found that targeted disruption of the entire Cables2 locus (Cables2d) caused growth retardation and enhanced apoptosis at the gastrulation stage and then induced embryonic lethality in mice. Comparative transcriptome analysis revealed disruption of Cables2, 50% down-regulation of Rps21 abutting on the Cables2 locus, and up-regulation of p53-target genes in Cables2d gastrulas. We further revealed the lethality phenotype in Rps21-deleted mice and unexpectedly, the exon 1-deleted Cables2 mice survived. Interestingly, chimeric mice derived from Cables2d ESCs carrying exogenous Cables2 and tetraploid wild-type embryo overcame gastrulation. These results suggest that the diminished expression of Rps21 and the completed lack of Cables2 expression are intricately involved in the embryonic lethality via the p53 pathway. This study sheds light on the importance of Cables2 locus in mouse embryonic development.Grant-in-Aid for Scientific Research(B), Japan Society for the Promotion of Science (JSPS KAKENHI 17H03568) Fumihiro Sugiyama Grant-in-Aid for Scientific Research(S), Japan Society for the Promotion of Science (JSPS KAKENHI 26221004) Satoru Takahashi Grant-in-Aid for Scientific Research(C), Japan Society for the Promotion of Science (JSPS KAKENHI 17K07130) Hiroyoshi Iseki Grant-in-Aid for Young Scientists (B), Japan Society for the Promotion of Science (JSPS KAKENHI 19K16020) Tra Thi Huong Dinh Grant-in-Aid for Scientific Research(A), Japan Society for the Promotion of Science (JSPS KAKENHI 20H00444) Fumihiro Sugiyama The Cooperative Research Project Program of Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA Center), University of Tsukuba, Japan (182107) Fumihiro Sugiyam

Simple generation of hairless mice for in vivo imaging

The in vivo imaging of mice makes it possible to analyze disease progress non-invasively through reporter gene expression. As the removal of hair improves the accuracy of in vivo imaging, gene-modified mice with a reporter gene are often crossed with Hos:HR-1 mutant mice homozygous for the spontaneous Hrhr mutation that exhibit a hair loss phenotype. However, it is time consuming to produce mice carrying both the reporter gene and mutant Hrhr gene by mating. In addition, there is a risk that genetic background of the gene-modified mice would be altered by mating. To resolve these issues, we established a simple method to generate hairless mice maintaining the original genetic background by CRISPR technology. First, we constructed the pX330 vector, which targets exon 3 of Hr. This DNA vector (5 ng/µl) was microinjected into the pronuclei of C57BL/6J mice. Induced Hr gene mutations were found in many founders (76.1%) and these mutations were heritable. Next, we performed in vivo imaging using these gene-modified hairless mice. As expected, luminescent objects in their body were detected by in vivo imaging. This study clearly showed that hairless mice could be simply generated by the CRISPR/Cas9 system, and this method may be useful for in vivo imaging studies with various gene-modified mice

Public health concerns for anti-obesity medicines imported for personal use through the internet: a cross-sectional study.

医薬保健研究域薬学系Objective: To explore the circulation of anti-obesity medicines via the internet and their quality. Design: Cross-sectional study. Setting: Internet pharmacies and pharmaceutical suppliers accessible from Japan. Participants: Anti-obesity medicines were purchased using relevant keywords on Japanese Google search engine. Blogs and advertisement-only sites were excluded. Primary and secondary outcome measures: The authenticity of the samples was investigated in collaboration with the manufacturers of the samples and medicine regulatory authorities. Quality of the samples was assessed by pharmacopoeial analyses using high-performance liquid chromatography. Results: 82 samples were purchased from 36 internet sites. Approximately half of the sites did not mention a physical address, and 45% of the samples did not contain a package insert. A variety of custom declarations were made for the shipments of the samples: personal health items, supplement, medicines, general merchandise, tea and others. Among 82 samples, 52 samples were analysed to check their pharmacopoeial quality. Authenticity responses were received from only five of 20 manufacturing companies. According to the pharmacopoeial analyses and authenticity investigation, three of the samples were identified as counterfeits and did not contain any active ingredients. Two of these samples were confirmed as counterfeits by the manufacturer of the authentic products. The manufacturer of the other sample did not respond to our request for an authenticity check even after several communication attempts. These counterfeit cases have been reported at the rapid alert system of Western Pacific Region of the WHO. Conclusions: Many counterfeit and unapproved anti-obesity medicines may be easily bypassing regulatory checks during shipping and are widely circulated through the internet. Regulatory authorities should take measures to prevent these medicines from entering countries to safeguard their citizens

Study on health hazards through medicines purchased on the Internet: a cross-sectional investigation of the quality of anti-obesity medicines containing crude drugs as active ingredients.

医薬保健研究域薬学系Background: Weight-loss medicines, including crude drugs and herbal supplements disguised as diet-aid products, are readily obtainable and distributed widely, especially in Southeast Asia. Even if such products are unapproved or prescription-only medicines, consumers can purchase them through an agency or directly on the Internet. We evaluated the quality and safety of herbal products purchased on the Internet to reveal their influence on public health. Methods: Diet-aid products containing Bukuryo (Poria sclerotium), Bakumondo (Ophiopogonis tuber), or Daio (rhubarb rhizome) were purchased through websites that did not provide physical addresses or which advertised misleading medicines (e.g., unapproved Cialis 100 mg tablets, Viagra 100 mg tablets) on websites. We carefully noted details in the descriptions on package inserts or accompanying product characteristics and analyzed the ingredients using qualitative and quantitative methods, namely high-performance liquid chromatography equipped with a photodiode array detector. We requested the respective manufacturers to authenticate their products through a structured questionnaire. Results: We purchased 15 items from 15 Internet sites and imported all 15 items to Japan. One item stated to contain rhubarb rhizome was identified as a prescription medicine; the others were dietary supplements and not medicines. Even though we did not analyze the constituents of all crude drugs, we found some active ingredients in the items. Sibutramine was detected in items confirmed to be supplements, including those containing Poria sclerotium and Ophiopogonis tuber. Each capsule contained ≈ 12 mg of sibutramine, which is the daily dose for anti-obesity medicines. Sibutramine is not approved for use in Japan and its sale has been suspended in Europe and the USA owing to serious adverse effects on the circulatory system. Conclusions: Our findings indicate that dietary supplements containing injurious ingredients are distributed to Japanese consumers and potentially to a broader international audience, and that purchasing them through unreliable websites bears potential health risks. To avoid potential adverse events, there should be adequate alerts about the risks of taking products without appropriate indications. © 2015 Yoshida et al

Correlation between emission property and concentration of Sn^2+ center in the SnO-ZnO-P_2O_5 glass

The authors report on the correlation between the photoluminescence (PL) property and the SnO amount in SnO-ZnO-P_2O_5 (SZP) glass. In the PL excitation (PLE) spectra of the SZP glass containing Sn^2+ emission center, two S_1 states, one of which is strongly affected by SnO amount, are assumed to exist. The PLE band closely correlates with the optical band edge originating from Sn^2+ species, and they both largely red-shifts with increasing amount of SnO. The emission decay time of the SZP glass decreased with increasing amount of SnO and the internal quantum efficiencies of the SZP glasses containing 1~5 mol% of SnO are comparable to that of MgWO_4. It is expected that the composition-dependent S_1 state (the lower energy excitation band) governs the quantum efficiency of the SZP glasses