Phase transition of zircon at high P-T conditions

In situ observations of the zircon-reidite transition in ZrSiO4 were carried out using a multianvil high-pressure apparatus and synchrotron radiation. The phase boundary between zircon and reidite was determined to be P (GPa) = 8.5 + 0.0017×(T-1200) (K) for temperatures between 1100-1900 K. When subducted slabs, including igneous rocks and sediments, descend into the upper mantle, zircon in the subducted slab transforms into reidite at pressures of about 9 GPa, corresponding to a depth of 270 km. Reidite found in an upper Eocene impact ejecta layer in marine sediments is thought to have been transformed from zircon by a shock event. The peak pressure generated by the shock event in this occurrence is estimated to be higher than 8 GPa

Thermal equation of state and thermodynamic properties of iron carbide Fe 3 C to 31 GPa and 1473 K

Resent experimental and theoretical studies suggested preferential stability of Fe 3 C over Fe 7 C 3 at the condition of the Earth's inner core. Previous studies showed that Fe 3 C remains in an orthorhombic structure with the space group Pnma to 250 GPa, but it undergoes ferromagnetic (FM) to paramagnetic (PM) and PM to nonmagnetic (NM) phase transitions at 6–8 and 55–60 GPa, respectively. These transitions cause uncertainties in the calculation of the thermoelastic and thermodynamic parameters of Fe 3 C at core conditions. In this work we determined P‐V‐T equation of state of Fe 3 C using the multianvil technique and synchrotron radiation at pressures up to 31 GPa and temperatures up to 1473 K. A fit of our P‐V‐T data to a Mie‐Gruneisen‐Debye equation of state produce the following thermoelastic parameters for the PM‐phase of Fe 3 C: V 0  = 154.6 (1) Å 3 , K T 0 = 192 (3) GPa, K T ′ = 4.5 (1), γ 0 = 2.09 (4), θ 0  = 490 (120) К, and q  = −0.1 (3). Optimization of the P‐V‐T data for the PM phase along with existing reference data for thermal expansion and heat capacity using a Kunc‐Einstein equation of state yielded the following parameters: V 0  = 2.327 cm 3 /mol (154.56 Å 3 ), K T 0  = 190.8 GPa, K T ′ = 4.68, Θ E10  = 305 K (which corresponds to θ 0  = 407 K), γ 0  = 2.10, e 0  = 9.2 × 10 −5 K −1 , m  = 4.3, and g  = 0.66 with fixed parameters m E 1  = 3 n  = 12, γ ∞  = 0, β  = 0.3, and a 0  = 0. This formulation allows for calculations of any thermodynamic functions of Fe 3 C versus T and V or versus T and P . Assuming carbon as the sole light element in the inner core, extrapolation of our equation of state of the NM phase of Fe 3 C suggests that 3.3 ± 0.9 wt % С at 5000 К and 2.3 ± 0.8 wt % С at 7000 К matches the density at the inner core boundary. Key Points We present a P‐V‐T EOS for PM‐Fe 3 C with support from thermodynamic analyses We discuss uncertainties in magnetic transitions We applied EOS data for modeling carbon content in the corePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101805/1/jgrb50396.pd

ERRγ agonist under mechanical stretching manifests hypertrophic cardiomyopathy phenotypes of engineered cardiac tissue through maturation

iPS細胞から成熟した人工心筋組織の作製方法の開発 肥大型心筋症の治療法開発への利用に期待. 京都大学プレスリリース. 2023-10-06.Stretching and stimulating engineered heart tissues to accurately portray hypertrophic cardiomyopathy. 京都大学プレスリリース. 2023-10-17.Engineered cardiac tissue (ECT) using human induced pluripotent stem cell-derived cardiomyocytes is a promising tool for modeling heart disease. However, tissue immaturity makes robust disease modeling difficult. Here, we established a method for modeling hypertrophic cardiomyopathy (HCM) malignant (MYH7 R719Q) and nonmalignant (MYBPC3 G115∗) pathogenic sarcomere gene mutations by accelerating ECT maturation using an ERRγ agonist, T112, and mechanical stretching. ECTs treated with T112 under 10% elongation stimulation exhibited more organized and mature characteristics. Whereas matured ECTs with the MYH7 R719Q mutation showed broad HCM phenotypes, including hypertrophy, hypercontraction, diastolic dysfunction, myofibril misalignment, fibrotic change, and glycolytic activation, matured MYBPC3 G115∗ ECTs displayed limited phenotypes, which were primarily observed only under our new maturation protocol (i.e., hypertrophy). Altogether, ERRγ activation combined with mechanical stimulation enhanced ECT maturation, leading to a more accurate manifestation of HCM phenotypes, including non-cardiomyocyte activation, consistent with clinical observations

Regulation of HGF-induced hepatocyte proliferation by the small GTPase Arf6 through the PIP2-producing enzyme PIP5K1A

HGF and its receptor c-Met are critical molecules in various biological processes. Others and we have previously shown that the small GTPase Arf6 plays a pivotal role in HGF signaling in hepatocytes. However, the molecular mechanism of how Arf6 regulates HGF signaling is unclear. Here, we show that Arf6 plays an important role in HGF-stimulated hepatocyte proliferation and liver regeneration through the phosphatidylinositol 4,5-bisphosphate (PIP2)-producing enzyme PIP5K1A. We find that knockdown of Arf6 and PIP5K1A in HepG2 cells inhibits HGF-stimulated proliferation, Akt activation, and generation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) and its precursor PIP2. Interestingly, PIP5K1A is recruited to c-Met upon HGF stimulation in an Arf6 activity-dependent manner. Finally, we show that hepatocyte proliferation and liver regeneration after partial hepatectomy are suppressed in Pip5k1a knockout mice. These results provide insight into the molecular mechanism for HGF-stimulated hepatocyte proliferation and liver regeneration: Arf6 recruits PIP5K1A to c-Met and activates it upon HGF stimulation to produce PIP2 and subsequently PIP3, which in turn activates Akt to promote hepatocyte proliferation, thereby accelerating liver regeneration after liver injury

Field Effect of Alcohol, Cigarette Smoking, and Their Cessation on the Development of Multiple Dysplastic Lesions and Squamous Cell Carcinoma: A Long-term Multicenter Cohort Study

[Background and Aims] Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients’ quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. [Methods] This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. [Results] LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0–57.2 and 13.3%, 95% CI = 8.1–21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26–0.85 and 0.49, 95% CI = 0.26–0.91, respectively). [Conclusion] Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676