Study on the reusability of fluorescent nuclear track detectors using optical bleaching

Fluorescent nuclear track detectors (FNTDs) based on Al${_2}$O${_3}$:C,Mg crystals are luminescent detectors that can be used for dosimetry and detection of charged particles and neutrons. These detectors can be utilised for imaging applications where a reasonably high track density, approximately of the order of 1 $\times$ $10^4$ tracks in an area of 100 $\times$ 100 $\mu$m$^2$, is required. To investigate the reusability of FNTDs for imaging applications, we present an approach to perform optical bleaching under the required track density conditions. The reusability was assessed through seven irradiation-bleaching cycles. For the irradiation, the studied FNTD was exposed to alpha-particles from an $^{241}$Am radioactive source. The optical bleaching was performed by means of ultraviolet laser light with a wavelength of 355 nm. Three dedicated regions on a single FNTD with different accumulated track densities and bleaching conditions were investigated. After every irradiation-bleaching cycle, signal-to-noise ratio was calculated to evaluate FNTD performance. It is concluded that FNTDs can be reused at least seven times for applications where accumulation of a high track density is required

FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters

乳がんの再発を起こす原因細胞を解明. 京都大学プレスリリース. 2023-11-16.The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain–containing ion transport regulator 3 (FXYD3), a component of the Na⁺/K⁺ pump. Accordingly, FXYD3⁺ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3⁺ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3⁺ CSCs were sensitive to senolytic Na⁺/K⁺ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3⁺ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na⁺/K⁺ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis

Enhancement of Both Long-Term Depression Induction and Optokinetic Response Adaptation in Mice Lacking Delphilin

In the cerebellum, Delphilin is expressed selectively in Purkinje cells (PCs) and is localized exclusively at parallel fiber (PF) synapses, where it interacts with glutamate receptor (GluR) δ2 that is essential for long-term depression (LTD), motor learning and cerebellar wiring. Delphilin ablation exerted little effect on the synaptic localization of GluRδ2. There were no detectable abnormalities in cerebellar histology, PC cytology and PC synapse formation in contrast to GluRδ2 mutant mice. However, LTD induction was facilitated at PF-PC synapses in Delphilin mutant mice. Intracellular Ca2+ required for the induction of LTD appeared to be reduced in the mutant mice, while Ca2+ influx through voltage-gated Ca2+ channels and metabotropic GluR1-mediated slow synaptic response were similar between wild-type and mutant mice. We further showed that the gain-increase adaptation of the optokinetic response (OKR) was enhanced in the mutant mice. These findings are compatible with the idea that LTD induction at PF-PC synapses is a crucial rate-limiting step in OKR gain-increase adaptation, a simple form of motor learning. As exemplified in this study, enhancing synaptic plasticity at a specific synaptic site of a neural network is a useful approach to understanding the roles of multiple plasticity mechanisms at various cerebellar synapses in motor control and learning

Novel method for producing very-neutron-rich hypernuclei via charge-exchange reactions with heavy ion projectiles

We propose a novel method for producing very-neutron-rich hypernuclei and corresponding resonance states by employing charge-exchange reactions via pp($$^{12}$$C, $$^{12}$$N $$K^+$$)n$$\varLambda$$ with single-charge-exchange and ppp($$^{9}$$Be, $$^{9}$$C $$K^+$$)nn$$\varLambda$$ with double-charge-exchange, both of which produce $$\varLambda K^+$$ in a target nucleus. The feasibility of producing very-neutron-rich hypernuclei using the proposed method was analysed by applying an ultra-relativistic quantum molecular dynamics model to a $$^6$$Li + $$^{12}$$C reaction at 2 A GeV. The yields of very-neutron-rich hypernuclei, signal-to-background ratios, and background contributions were investigated. The proposed method is a powerful tool for studying very-neutron-rich hypernuclei and resonance states with a hyperon for experiments employing the Super-FRS facility at FAIR and HFRS facility at HIAF

Strain-Induced Martensitic Transformation and Texture Evolution in Cold-Rolled Co–Cr Alloys

Co–Cr alloys have been used in biomedical purposes such as stents and artificial hip joints. However, the difficulty of plastic deformation limits the application of the alloys. During the deformation, Co–Cr alloys often exhibit strain-induced martensitic transformation (SIMT), which is a possible reason for the low formability. The distinct increase in dislocation density in the matrix phase may also result in early fractures. Since these microstructural evolutions accompany the textural evolution, it is crucial to understand the relationship among the SIMT, the increase in dislocations, and the texture evolution. To characterize those at the same time, we conducted time-of-flight neutron diffraction experiments at iMATERIA beamline at the Japan Proton Accelerator Research Complex (J-PARC) Materials and Life Science Experimental Facility (MLF), Ibaraki, Japan. The cold-rolled sheets of Co–29Cr–6Mo (CCM) and Co–20Cr–15W–10Ni (CCWN) alloys were investigated in this study. As expected from the different stacking fault energies, the SIMT progressed more rapidly in the CCM alloy. The dislocation densities of the matrix phases of the CCM and CCWN alloys increased similarly with an increase in the rolling reduction. These results suggest that the difference in deformability between the CCM and CCWN alloys originate not from the strain hardening of the matrix phase but from the growth behaviors of the martensitic phase

Crucial Role of Elovl6 in Chondrocyte Growth and Differentiation during Growth Plate Development in Mice

<div><p>ELOVL family member 6, elongation of very long chain fatty acids (Elovl6) is a microsomal enzyme, which regulates the elongation of C12-16 saturated and monounsaturated fatty acids. Elovl6 has been shown to be associated with various pathophysiologies including insulin resistance, atherosclerosis, and non-alcoholic steatohepatitis. To investigate a potential role of Elovl6 during bone development, we here examined a skeletal phenotype of <i>Elovl6</i> knockout (<i>Elovl6</i>^<i>-/-</i>) mice. The <i>Elovl6</i>^<i>-/-</i> skeleton was smaller than that of controls, but exhibited no obvious patterning defects. Histological analysis revealed a reduced length of proliferating and an elongated length of hypertrophic chondrocyte layer, and decreased trabecular bone in <i>Elovl6</i>^<i>-/-</i> mice compared with controls. These results were presumably due to a modest decrease in chondrocyte proliferation and accelerated differentiation of cells of the chondrocyte lineage. Consistent with the increased length of the hypertrophic chondrocyte layer in <i>Elovl6</i>^<i>-/-</i> mice, <i>Collagen10</i>α<i>1</i> was identified as one of the most affected genes by ablation of <i>Elovl6</i> in chondrocytes. Furthermore, this elevated expression of <i>Collagen10α1</i> of Elovl6-null chondrocytes was likely associated with increased levels of <i>Foxa2/a3</i> and <i>Mef2c</i> mRNA expression. Relative increases in protein levels of nuclear Foxa2 and cytoplasmic histone deacethylase 4/5/7 were also observed in <i>Elovl6</i> knockdown cells of the chondrocyte lineage. Collectively, our data suggest that Elovl6 plays a critical role for proper development of embryonic growth plate.</p></div

Lack of <i>Elovl6</i> altered fatty acid composition in costal primary chondrocytes.

<p>(A) Lack of <i>Elovl6</i> significantly increases C16:0 and decreases C18:1 (n-9) in primary chondrocytes. Gas chromatography analysis was performed to examine fatty acid composition of primary chondrocytes harvested from <i>control</i> and <i>Elovl6</i>^<i>-/-</i> mice (n = 3 in each group). (B) Lack of <i>Elovl6</i> significantly decreases <i>Scd-2</i> mRNA levels in primary chondrocyte. Quantitative determination of levels of <i>Scd-1</i> and <i>Scd-2</i> mRNA was examined by real-time qPCR (n = 4 in each group). *p < 0.05, **p < 0.01, ***p < 0.005 vs. controls.</p

Knockdown of <i>Elovl6</i> in ATDC5 cells increased nuclear localization of Foxa2.

<p>(A) Western blot analysis of Foxa2 using cytoplasmic and nuclear extracts isolated from control and <i>Elovl6</i>-KD ATDC5 cells after an incubation of the cells in a differentiation medium for 7 days. (B) Quantitative analysis of the intensity of Foxa2 bands in reference to those of Lamin A/C. *p < 0.05 vs. controls.</p

Knockdown of <i>Elovl6</i> in ATDC5 cells promoted cytoplasmic localization of HDAC4/5/7.

<p>(A, B) Knockdown of <i>Elovl6</i> significantly decreases expression of <i>HDACs 4</i> (A, B), <i>5</i> and <i>7</i> (B) mRNA in ATDC5 cells (n = 3 in each group). (C) Representative images of Western blot analysis of HDAC4/5/7 using cytoplasmic and nuclear extracts isolated from control and <i>Elovl6</i>-KD ATDC5 cells after an incubation of the cells in a differentiation medium for 7 days. (B) Quantitative analysis of the intensity of HDAC4/5/7 bands in reference to those of α-Tubulin for cytoplasmic and Lamin A/C for nuclear extracts. *p < 0.05, **p < 0.01, ***p < 0.005, ****p<0.001 vs. controls.</p

Knockdown of <i>Elovl6</i> in mouse chondrogenic ATDC5 cells modified levels of expression of <i>Col10α1</i> and its related transcription factors.

<p>(A) Knockdown of <i>Elovl6</i> significantly increases C16:0 and decreases C18:1 (n-9) in ATDC5 cells (n = 4 in each group). (B) Knockdown of <i>Elovl6</i> significantly decreases expression of <i>Scd-1</i> and <i>Scd-2</i> in ATDC5 cells (n = 3 in each group). (C) Knockdown of <i>Elovl6</i> significantly increases gene expression of <i>Col10α1</i> in a time-dependent manner. Control and <i>Elovl6</i>-KD ATDC5 cells were cultured in a differentiation medium for 0, 4, 7, and 10 days after cells reached a plateau. (D) Relative mRNA levels of marker genes for chondrocyte differentiation, were determined by real-time qPCR (n = 3–9 in each group). *p < 0.05, **p < 0.01, ***p < 0.005, ****p<0.001 vs. controls.</p