Dynamic collision behavior between osteoblasts and tumor cells regulates the disordered arrangement of collagen fiber/apatite crystals in metastasized bone

Bone metastasis is one of the most intractable bone diseases; it is accompanied with a severe mechanical dysfunction of bone tissue. We recently discovered that the disorganized collagen/apatite microstructure in cancer-bearing bone is a dominant determinant of the disruption of bone mechanical function; disordered osteoblast arrangement was found to be one of the principal determinants of the deteriorated collagen/apatite microstructure. However, the precise molecular mechanisms regulating the disordered osteoblast arrangement triggered by cancer invasion are not yet understood. Herein, we demonstrate a significant disorganization of bone tissue anisotropy in metastasized bone in our novel ex vivo metastasis model. Further, we propose a novel mechanism underlying the disorganization of a metastasized bone matrix: A dynamic collision behavior between tumor cells and osteoblasts disturbs the osteoblast arrangement along the collagen substrate.Matsugaki A., Harada T., Kimura Y., et al. Dynamic collision behavior between osteoblasts and tumor cells regulates the disordered arrangement of collagen fiber/apatite crystals in metastasized bone. International Journal of Molecular Sciences, 19, 11, 3474. https://doi.org/10.3390/ijms19113474

Fire behaviour of non-load bearing double stud cold-formed steel frame walls

This work investigates the behaviour of Double stud Light Steel Frame (LSF) walls under ISO834 standard fire through a series of experimental tests. The walls were covered on both sides with one or two fire-resistant gypsum plasterboards (Type F), and the cavity of the steel frame was either empty, partially or fully insulated with ceramic fibre. The fire resistance of the assemblies is improved due to the existence of a wider cavity, the employment of additional gypsum plasterboard layers and the use of ceramic fibre cavity insulation. In partially insulated assemblies, significantly higher fire resistance is achieved when the ceramic fibre is placed towards the fire-exposed gypsum plasterboard. Moreover, the number of studs in contact with the unexposed gypsum plasterboard affects the fire resistance of the specimens. The experimental data acquired is useful to conduct further numerical analyses and experimental studies, as well as to understand the unique thermal behaviour of different configurations of double stud LSF walls at elevated temperatures.info:eu-repo/semantics/publishedVersio

Changes in Lysosomal Enzyme Activities in Rat Liver Following Partial Hepatectomy.

The changes in lysosomal enzyme activities in rat liver after partial hepatectomy were studied with the whole liver and isolated hepatocyte suspension. The activity patterns of enzymes were different between the stages before and after mitosis, and also between the two cell types of hepatocytes and non-hepatocytes in the liver. Increase of enzyme activities, especially of acid ribonuclease, in the premitotic stage suggests that the lysosomes may participate in the cell division during liver regeneration

精神疾患を有する人への「リカバリーゼミ」の実践～参加者の語りからの評価～

精神疾患を有し精神科デイケアや就労支援などの社会資源につながっていない人へのリカバリー支援としてのプログラム「リカバリーゼミ」を実施した。本研究の目的は、本実践が参加者のリカバリー推進に寄与できたのかを考察することである。研究対象者は5 名で、いずれもひきこもり傾向や何らかの依存傾向があった。実施期間は2015 年5 月～ 2016 年6 月で、基本的に月2 回、1 回2 時間のクローズドグループで実施した。結果はRecovery Assessment Scale：RAS の点数が、参加者5 人中4 名終了時に上昇していた。また、生活も参加者の望む方向へ変化していた。このことより「グループ学習や体験を通して参加者が自身の人生を前向きに捉え、自身の責任において自身の希望や目的に向かって、人生の歩みを進める一助となること」という本プログラムの目的を概ね達成し、各人のリカバリー推進に寄与できたと考える

Identification of the ultrahigh-risk subgroup in neuroblastoma cases through DNA methylation analysis and its treatment exploiting cancer metabolism

神経芽腫の新たな診断法と治療戦略を創出 --がん細胞の生存戦略「がん代謝」を逆用する--. 京都大学プレスリリース. 2022-11-02.Neuroblastomas require novel therapies that are based on the exploitation of their biological mechanism. To address this need, we analyzed the DNA methylation and expression datasets of neuroblastomas, extracted a candidate gene characterizing the aggressive features, and conducted functional studies. Based on the DNA methylation data, we identified a subgroup of neuroblastoma cases with 11q loss of heterozygosity with extremely poor prognosis. PHGDH, a serine metabolism-related gene, was extracted as a candidate with strong expression and characteristic methylation in this subgroup as well as in cases with MYCN amplification. PHGDH inhibition suppressed neuroblastoma cell proliferation in vitro and in vivo, indicating that the inhibition of serine metabolism by PHGDH inhibitors is a therapeutic alternative for neuroblastoma. Inhibiting the arginine metabolism, which is closely related to serine metabolism using arginine deiminase, had a combination effect both in vitro and in vivo, especially on extracellular arginine-dependent neuroblastoma cells with ASS1 deficiency. Expression and metabolome analyses of post-dose cells confirmed the synergistic effects of treatments targeting serine and arginine indicated that xCT inhibitors that inhibit cystine uptake could be candidates for further combinatorial treatment. Our results highlight the rational therapeutic strategy of targeting serine/arginine metabolism for intractable neuroblastoma

The Shock State of Itokawa Sample

One of the fundamental aspects of any astromaterial is its shock history, since this factor elucidates critical historical events, and also because shock metamorphism can alter primary mineralogical and petrographic features, and reset chronologies [1]. Failure to take shock history into proper account during characterization can result in seriously incorrect conclusions being drawn. Thus the Hayabusa Preliminary Examination Team (HASPET) made shock stage determination of the Itokawa samples a primary goal [2]. However, we faced several difficulties in this particular research. The shock state of ordinary chondrite materials is generally determined by simple optical petrographic observation of standard thin sections. The Itokawa samples available to the analysis team were mounted into plastic blocks, were polished on only one side, and were of non-standard and greatly varying thickness, all of which significantly complicated petrographic analysis but did not prevent it. We made an additional estimation of the sample shock state by a new technique for this analysis - electron back-scattered diffraction (EBSD) in addition to standard petrographic techniques. We are also investigating the crystallinity of Itokawa olivine by Synchrotron X-ray diffraction (SXRD)

Cathepsin K activity controls cardiotoxin‐induced skeletal muscle repair in mice

Abstract Background: Cathepsin K (CatK) is a widely expressed cysteine protease that has gained attention because of its enzymatic and non‐enzymatic functions in signalling. Here, we examined whether CatK‐deficiency (CatK−/−) would mitigate injury‐related skeletal muscle remodelling and fibrosis in mice, with a special focus on inflammation and muscle cell apoptosis. Methods: Cardiotoxin (CTX, 20 μM/200 μL) was injected into the left gastrocnemius muscle of male wild‐type (CatK+/+) and CatK−/− mice, and the mice were processed for morphological and biochemical studies. Results: On post‐injection Day 14, CatK deletion ameliorated muscle interstitial fibrosis and remodelling and performance. At an early time point (Day 3), CatK−/− reduced the lesion macrophage and leucocyte contents and cell apoptosis, the mRNA levels of monocyte chemoattractant protein‐1, toll‐like receptor‐2 and toll‐like receptor‐4, and the gelatinolytic activity related to matrix metalloproteinase‐2/‐9. CatK deletion also restored the protein levels of caspase‐3 and cleaved caspase‐8 and the ratio of the BAX to the Bcl‐2. Moreover, CatK deficiency protected muscle fibre laminin and desmin disorder in response to CTX injury. These beneficial muscle effects were mimicked by CatK‐specific inhibitor treatment. In vitro experiments demonstrated that pharmacological CatK inhibition reduced the apoptosis of C2C12 mouse myoblasts and the levels of BAX and caspase‐3 proteins induced by CTX. Conclusions: These results demonstrate that CatK plays an essential role in skeletal muscle loss and fibrosis in response to CTX injury, possibly via a reduction of inflammation and cell apoptosis, suggesting a novel therapeutic strategy for the control of skeletal muscle diseases by regulating CatK activity

Dynamic Regulation of Myosin Light Chain Phosphorylation by Rho-kinase

Myosin light chain (MLC) phosphorylation plays important roles in various cellular functions such as cellular morphogenesis, motility, and smooth muscle contraction. MLC phosphorylation is determined by the balance between activities of Rho-associated kinase (Rho-kinase) and myosin phosphatase. An impaired balance between Rho-kinase and myosin phosphatase activities induces the abnormal sustained phosphorylation of MLC, which contributes to the pathogenesis of certain vascular diseases, such as vasospasm and hypertension. However, the dynamic principle of the system underlying the regulation of MLC phosphorylation remains to be clarified. Here, to elucidate this dynamic principle whereby Rho-kinase regulates MLC phosphorylation, we developed a mathematical model based on the behavior of thrombin-dependent MLC phosphorylation, which is regulated by the Rho-kinase signaling network. Through analyzing our mathematical model, we predict that MLC phosphorylation and myosin phosphatase activity exhibit bistability, and that a novel signaling pathway leading to the auto-activation of myosin phosphatase is required for the regulatory system of MLC phosphorylation. In addition, on the basis of experimental data, we propose that the auto-activation pathway of myosin phosphatase occurs in vivo. These results indicate that bistability of myosin phosphatase activity is responsible for the bistability of MLC phosphorylation, and the sustained phosphorylation of MLC is attributed to this feature of bistability

Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology