キラル医薬品製造技術の進歩 ―分子認識を制御する新しい光学分割技術―

結晶化を経由する光学分割法は、およそ170年以前に発見された技術であるが、現在もなお実験室や工業規模で光学活性な化合物を製造する技術として有効活用されている。中でも「ジアステレオマー塩形成法」は医薬品、農薬、液晶など様々な分野の光学活性物質製造技術として適用されている。しかし、これまで幾多の報告や特許がなされてきたにも関わらず、これらの技術に関する確固たる理論は確立されてこなかった。著者らは、光学活性物質の製造技術開発の中で、これまで知られていなかった技術や理論を開発した。以下我々が発見・開発した以下の３つの技術・理論を紹介する。（1）設計したキラル添加物を用いた「結晶形態制御」による光学純度の改善法、（2）作業理論「空間充填コンセプト」に基づく最適分割剤の新しい選択法、（3）「誘電率制御光学分割」によるキラリティー制御法

Transcription element responsible for the brain cell-specific expression of the Bombyxin gene that encodes an insect insulin-related peptide

金沢大学理工研究域自然システム学系Invertebrate insulin-related peptides play key roles in growth and metabolism. Genes encoding these peptides are specifically expressed in neurosecretory cells. Bombyxin genes of the silkmoth Bombyx mori encode insulin-related peptides and are expressed in four pairs of the neurosecretory cells in pars intercerebralis of brain. No regulatory element has been identified to confer the neurosecretory cell-specific expression of bombyxin gene. By promoter-deletion analysis and in vitro electroporation, we identified a transcription element essential for the cell-specific expression of bombyxin F1 gene, one of the bombyxin multifamily genes. The element was localized in the region from -170 to -159 bp upstream of the translation start site of the F1 gene. We named the element as BOSE, BOmbyxin gene-Specific Element. No protein that would bind to BOSE was found by searching the transcription factors database. In addition, an activator element responsible for increasing the expression level was identified in the region from -185 to -181 bp. The activator element is similar to the core element in gut-specific enhancer region of the mosquito Anopeles gambiae trypsin gene and the element essential for expression of a Bombyx chorion gene

Co-infection of SARS-CoV-2 and influenza virus causes more severe and prolonged pneumonia in hamsters

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a serious public health concern worldwide. Notably, co-infection with other pathogens may worsen the severity of COVID-19 symptoms and increase fatality. Here, we show that co-infection with influenza A virus (IAV) causes more severe body weight loss and more severe and prolonged pneumonia in SARS-CoV-2-infected hamsters. Each virus can efficiently spread in the lungs without interference by the other. However, in immunohistochemical analyses, SARS-CoV-2 and IAV were not detected at the same sites in the respiratory organs of co-infected hamsters, suggesting that either the two viruses may have different cell tropisms in vivo or each virus may inhibit the infection and/or growth of the other within a cell or adjacent areas in the organs. Furthermore, a significant increase in IL-6 was detected in the sera of hamsters co-infected with SARS-CoV-2 and IAV at 7 and 10 days post-infection, suggesting that IL-6 may be involved in the increased severity of pneumonia. Our results strongly suggest that IAV co-infection with SARS-CoV-2 can have serious health risks and increased caution should be applied in such cases

Preliminary Survey to Establish Indicator for Screening of Primary School-age Children Who Require Welfare Assistance

小学校において被虐待児にみられる行動特徴から要保護児童をスクリーニングできる質問紙を作成するために，教職員にとって判断が容易で信頼性の高い回答が得られる項目を厳選するための基礎調査を行った。64名の小学校の教職員に，35項目からなる同じ内容の質問紙に2週間の間隔をあけ， 2回回答してもらった結果を照合し，質問内容の判断の容易さ回答の再現性，および文章表現について検討した。 1. 学校現場で教職員が判断するのが難しい質問項目は，「トイレの後に手を洗わない」，「行事の時の弁当が手作り弁当ではない」，「保護者と目を合わさず，おどおどする」，「家族関係に変化があった」，「年齢にそぐわない性的な言動がみられる」，「病気になっても病院に行かない」，および「過度な警戒心を持つ」であった。 2. 回答の信頼性の低い質問項目は「やせすぎている」，「行事の時の弁当が手作り弁当ではない」，「よく教室から離れる」，および「保護者と目を合わさず，おどおどする」であった。 3. 表現が不適切であると指摘された質間項目は「時々嘘をつく」，「友達をいじめる」，および「集団になじめないところがある」であった。 今後は，上記の質問項目を除いた質問項目からなる質問紙を作成し，実際に児童を対象とした調査を行い，要保護児童のスクリーニング指標としての有効性について検証する必要があると考えられる。We conducted a survey to select questions that teachers could easily and reliably answer as part of a basic research project to create a questionnaire based on characteristic behaviors exhibited by abused children at primary school for screening of those who may need welfare assistance. Questionnaires comprised of 35 items were sent to 64 primary school teachers, with the same questionnaire sent again 2 weeks later. Responses to both were compared to examine ease of assessing the contents of the questions, reproducibility of the responses, and written expressions. 1) Items that teachers found difficult to assess at school were "Does not wash hands after using the toilet," "Does not bring homemade lunch to events," "Does not meet guardian's eyes; appears apprehensive," "Has experienced a change in familial relations," "Uses sexual speech and behavior that is not age appropriate," "Does not see a doctor despite being sick," and "Is excessively wary." 2) Items that showed responses with low reliability were "ls too thin," "Does not bring homemade lunch to events," "Is often absent from the classroom," and "Does not meet guardian's eyes; appears apprehensive." 3) Items indicated to use inappropriate expressions were "Sometimes tells lies," "ls bullied by friends," and "Does not fit in with group in some ways." Next, use of a questionnaire that does not include the above items should be done with actual children to examine its effectiveness as an indicator for screening children who require welfare assistance

ホスピス トクシマ ニオケル マッキ ガン カンジャ ノ ボウシュヨウセイ シンケイ ショウコウグン ノ ハッショウ ヒンド ト ソノ リンショウテキ イギ

Neurological complications in advanced cancer occur frequently and therefore an adequate neurological assessment must always be part of patient evaluation in hospice palliative care. Paraneoplastic neurological syndromes are rare, probably affecting less than 1 per cent of patients with cancer, even if the most commonly associated neoplasms, such as small-cell lung cancer and ovarian cancer are considered. Neurological complications were studied in 127 inpatients with advanced cancers. Neurological complications were seen in up to 40 per cent of the patients. The most frequent symptom was derilium, followed in order to lethargy, paraplegia, depression, dementia, hemiplegia, restlessness, aphasia, stupor, facial palsy, recurrent laryngeal nerve palsy, convulsion, and myastenia. Those symptoms were seen in patients in hepatic encephalitis（12）, metastatic brain tumor（9）, metastatic spinal cord injury（8）, depression（4）, paraneoplastic syndrome（4）, hypercalcemia（2）, senile dementia（2）, peripheral neuritis（2）, and cerebral infarction（2）. Of the four patients with paraneoplastic syndrome, one patient had both anti-Hu antibody and anti-VGCC antibody and two patients had anti-neuronal nuclear antibodies. These results indicate that paraneoplastic neurological syndromes are associated more than 1 per cent of patients with advanced cancer

Evolutionary histories of breast cancer and related clones

乳がん発生の進化の歴史を解明 --ゲノム解析による発がんメカニズムの探索--. 京都大学プレスリリース. 2023-07-28.Tracking the ol' mutation trail: Unraveling the long history of breast cancer formation. 京都大学プレスリリース. 2023-08-31.Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1, 2, 3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient’s early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves

Monitor of All-sky X-ray Image (MAXI)

Abstract. Monitor of All-sky X-ray Image (MAXI) is the first astrophysical payload which will be mounted on the Japanese Experiment Module (JEM) Exposed Facility in 2004. It is an X-ray all-sky monitor with unprecedented sensitivity to watch the activities of the X-ray sources in the whole sky in every 90 minutes. MAXI is boxshaped in 0.8 x 1.0 x 1.85 m with the weight of 500 kg. The mission life will be at least 2 years. MAXI has two fan-like field of views (FOV), 160 x 1.5 degree each. The X-ray instruments are Gas Slit Camera (GSC) and Solid-state Slit Camera (SSC). The GSC uses gas one-dimensional position sensitive proportional counters with 5340 cm 2 effective area in total and the SSC uses CCDs with 200 cm 2 . Both are capable to detect one-dimensional image, which is used to obtain the locations of the X-ray sources in the FOV along the long direction. Together with the scan which determine the other direction, MAXI can scan almost all sky with a precision of better than 1 degree in the energy range of 0.5-30 keV. The CCD is electrically cooled to -60°C and the camera body is radiatively cooled to -20°C. The CCD chip itself and the radiators may suffer contamination problem. The continuous Ethernet down link will enable us to alert the astronomers in all over the world to the appearance of X-ray transients, novae, bursts, flares etc. We made a test counter and test chips in 1998. Those are being tested in RIKEN, NASDA and Osaka-university. In this paper the test results will be presented, as well as the general description of the MAXI mission

Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana

We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is ~32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene