A dynamic structural unit of phase-separated heterochromatin protein 1α as revealed by integrative structural analyses

ヘテロクロマチンタンパク質による液-液相分離機構を解明. 京都大学プレスリリース. 2025-03-24.The heterochromatin protein HP1α consists of an N-terminal disordered tail (N-tail), chromodomain (CD), hinge region (HR), and C-terminal chromo shadow domain (CSD). While CD binds to the lysine9-trimethylated histone H3 (H3K9me₃) tail in nucleosomes, CSD forms a dimer bridging two nucleosomes with H3K9me₃. Phosphorylation of serine residues in the N-tail enhances both H3K9me₃ binding and liquid–liquid phase separation (LLPS) by HP1α. We have used integrative structural methods, including nuclear magnetic resonance, small-angle X-ray scattering (SAXS), and multi-angle-light scattering combined with size-exclusion chromatography, and coarse-grained molecular dynamics simulation with SAXS, to probe the HP1α dimer and its CSD deletion monomer. We show that dynamic intra- and intermolecular interactions between the N-tails and basic segments in CD and HR depend on N-tail phosphorylation. While the phosphorylated HP1α dimer undergoes LLPS via the formation of aggregated multimers, the N-tail phosphorylated mutant without CSD still undergoes LLPS, but its structural unit is a dynamic intermolecular dimer formed via the phosphorylated N-tail and a basic segment at the CD end. Furthermore, we reveal that mutation of this basic segment in HP1α affects the size of heterochromatin foci in cultured mammalian cells, suggesting that this interaction plays an important role in heterochromatin formation in vivo

Non-maintenance intravesical Bacillus Calmette-Guerin induction therapy with eight doses in patients with high- or highest-risk non-muscle invasive bladder cancer: a retrospective non-randomized comparative study

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Functional Neurons Generated from T Cell-Derived Induced Pluripotent Stem Cells for Neurological Disease Modeling

Modeling of neurological diseases using induced pluripotent stem cells (iPSCs) derived from the somatic cells of patients has provided a means of elucidating pathogenic mechanisms and performing drug screening. T cells are an ideal source of patient-specific iPSCs because they can be easily obtained from samples. Recent studies indicated that iPSCs retain an epigenetic memory relating to their cell of origin that restricts their differentiation potential. The classical method of differentiation via embryoid body formation was not suitable for T cell-derived iPSCs (TiPSCs). We developed a neurosphere-based robust differentiation protocol, which enabled TiPSCs to differentiate into functional neurons, despite differences in global gene expression between TiPSCs and adult human dermal fibroblast-derived iPSCs. Furthermore, neurons derived from TiPSCs generated from a juvenile patient with Parkinson\u27s disease exhibited several Parkinson\u27s disease phenotypes. Therefore, we conclude that TiPSCs are a useful tool for modeling neurological diseases

Micro-milling super-fine powdered activated carbon decreases adsorption capacity by introducing oxygen/hydrogen-containing functional groups on carbon surface from water

Superfine powdered activated carbon (SPAC) of micron to submicron particle size is produced by micro-milling of conventionally sized powdered activated carbon. SPAC has attracted attention because of its high adsorption capacity; however, milling to the submicron particle size range lowers its adsorption capacity. Here, we found that this decrease of adsorption capacity was due to the introduction of oxygen/hydrogen containing functional groups into the graphene structure of the carbon from water during the milling, causing it to become less hydrophobic. This finding was supported by three analyses of SPAC particles before and after milling: 1) elemental analysis revealed increased oxygen and hydrogen content, 2) Boehm titration analysis revealed increased amounts of acidic functional groups, including carboxylic and phenolic hydroxyl groups, and 3) Fourier-transform infrared spectroscopy showed increased peaks at 1200, 1580, and 3400 cm−1, confirming the presence of those groups. Dissolved oxygen concentration did not strongly affect the increase of oxygen content in SPAC, and no evidence was found for hydroxyl radical production during micro-milling, suggesting that a mechanochemical reaction underlies the increase in oxygen/hydrogen-containing functional groups. An increase in 18O content in the SPAC particles after milling in water-18O indicated that the oxygen in the functional groups originated from the surrounding water

Zn protoporphyrin IX is formed not from heme but from protoporphyrin IX

We examined the effects of exogenous myoglobin, a bivalent chelator, and nitrite on Zn protoporphyrin IX (ZPP) formation by using model systems. ZPP was formed in a model solution without addition of exogenous myoglobin. After incubation, the amount of ZPP in a model solution was increased but that of heme was not decreased compared with the amounts before incubation. Protoporphyrin IX (PPIX) instead of ZPP also accumulated in a model solution with addition of EDTA, but the amount of heme was not reduced. These results suggested that ZPP was not formed by the Fe-Zn substitution in heme but was formed by the insertion of Zn into PPIX, which was formed independently. The fact that the effects of various factors in model systems with/without addition of a bivalent chelator were similar suggested that ZPP formation was strongly affected by PPIX formation. Inhibition of PPIX formation by nitrite might be the reason for the low levels of ZPP in cured meats

An interpretation of thermo-mechanical behaviour of peat under 1-D compression

The one-dimensional thermo-mechanical behaviour of two peats was investigated through consolidation tests, including incremental loadings and constant-rate-of-strain loadings, under a variety of temperature-stress conditions. As an appropriate expression of highly compressible materials, the natural strain was employed instead of conventional engineering strain, which eliminates the apparent stress dependency of the compression index and the coefficient of secondary compression. Test results suggest the applicability of an isotach approach to the two peats used in this study. The temperature dependency of the coefficient of secondary compression defined with natural strain, λ*α, is very small. All the results summarized on the effective stress-strain plane show that there exists a unique Normal Compression Line (NCL) corresponding to each combination of temperature and strain rate. The NCLs are parallel to each other. Finally, in an attempt to construct a constitutive model, the temperature dependency of the NCL was quantified by introducing a constant, λ*T. By using the two parameters, λ*α and λ*T, which describe the strain rate- and temperature-dependent characteristics, respectively, a 1-D thermo-mechanical behaviour observed in this study will be modelled in a simple manner

An interpretation of thermo-mechanical behaviour of peat under 1-D compression

The one-dimensional thermo-mechanical behaviour of two peats was investigated through consolidation tests, including incremental loadings and constant-rate-of-strain loadings, under a variety of temperature-stress conditions. As an appropriate expression of highly compressible materials, the natural strain was employed instead of conventional engineering strain, which eliminates the apparent stress dependency of the compression index and the coefficient of secondary compression. Test results suggest the applicability of an isotach approach to the two peats used in this study. The temperature dependency of the coefficient of secondary compression defined with natural strain, λ*α, is very small. All the results summarized on the effective stress-strain plane show that there exists a unique Normal Compression Line (NCL) corresponding to each combination of temperature and strain rate. The NCLs are parallel to each other. Finally, in an attempt to construct a constitutive model, the temperature dependency of the NCL was quantified by introducing a constant, λ*T. By using the two parameters, λ*α and λ*T, which describe the strain rate- and temperature-dependent characteristics, respectively, a 1-D thermo-mechanical behaviour observed in this study will be modelled in a simple manner

Effects of decreasing activated carbon particle diameter from 30 mu m to 140 nm on equilibrium adsorption capacity

The capacity of activated carbon particles with median diameters (D50s) of >similar to 1 mu m for adsorption of hydrophobic micropollutants such as 2-methylisolborneol (MIB) increases with decreasing particle size because the pollutants are adsorbed mostly on the exterior (shell) of the particles owing to the limited diffusion penetration depth. However, particles with D50s of <1 mu m have not been thoroughly investigated. Here, we prepared particles with D50s of similar to 30 mu m-similar to 140 nm and evaluated their adsorption capacities for MIB and several other environmentally relevant adsorbates. The adsorption capacities for low-molecular-weight adsorbates, including MIB, deceased with decreasing particle size for D50s of less than a few micrometers, whereas adsorption capacities increased with decreasing particle size for larger particles. The oxygen content of the particles increased substantially with decreasing particle size for D50s of less than a few micrometers, and oxygen content was negatively correlated with adsorption capacity. The decrease in adsorption capacity with decreasing particle size for the smaller particles was due to particle oxidation during the micromilling procedure used to decrease D50 to similar to 140 nm. When oxidation was partially inhibited, the MIB adsorption capacity decrease was attenuated. For high molecular-weight adsorbates, adsorption capacity increased with decreasing particle size over the entire range of tested particle sizes, even though particle oxygen content increased with decreasing particle size