Heme sensor proteins function in response to the availability of the heme iron complex. The heme iron complex per se becomes the first signal for various important physiological functions of these ...proteins. The role of the heme iron complex in heme sensors is distinct from those of prototype heme proteins, such as hemoglobin, cytochromes c and P450, in which the heme iron complex is the functional center. For heme sensor proteins, association/dissociation of the heme iron complex regulates physiological processes, including catalysis, transcription, and other functions essential for cell survival. Importantly, the main binding/sensing site of the heme iron complex in heme sensor proteins is cysteine thiolate, which is critical for the heme sensing function. The role of the cysteine thiolate in heme sensor proteins differs from that of the P450 system, in which the cysteine thiolate donates an electron to activate molecular oxygen bound to the heme iron complex trans to cysteine thiolate to facilitate the monooxygenase reaction. In this review, we discuss heme proteins with cysteine thiolate as the heme axial ligand, and summarize recent studies on heme sensor proteins and their molecular mechanisms. In particular, we focus on the controversial role of the heme iron complex in transcriptional regulation associated with circadian rhythms.
Cysteine thiolate is the Fe(III) heme sensing site for the heme sensor protein.
The heme sensor protein is flexible.
Imagine that the HRI protein acts as a hand in motion and uses the index finger and thumb to pick up the Fe(III) heme. Display omitted
Hypertensive cardiac remodeling is characterized by left ventricular hypertrophy and interstitial fibrosis, which can lead to heart failure with preserved ejection fraction. The Rho-associated ...coiled-coil containing kinases (ROCKs) are members of the serine/threonine protein kinase family, which mediates the downstream effects of the small GTP-binding protein RhoA. There are 2 isoforms: ROCK1 and ROCK2. They have different functions in different types of cells and tissues. There is growing evidence that ROCKs contribute to the development of cardiovascular diseases, including cardiac fibrosis, hypertrophy, and subsequent heart failure. Recent experimental studies using ROCK inhibitors, such as fasudil, have shown the benefits of ROCK inhibition in cardiac remodeling. Mice lacking each ROCK isoform also exhibit reduced myocardial fibrosis in a variety of pathological models of cardiac remodeling. Indeed, clinical studies with fasudil have suggested that ROCKs could be potential novel therapeutic targets for cardiovascular diseases. In this review, we summarize the current understanding of the roles of ROCKs in the development of cardiac fibrosis and hypertrophy and discuss their therapeutic potential for deleterious cardiac remodeling. (Circ J 2016; 80: 1491–1498)
Already, there are several processes to produce intermetalic alloy parts from powder , ex. metal injection molding (MIM) or additive manufacturing (AM). For these processes, pre-alloyed powder made ...by gas atomized powder is used because of their quality. As other way, intermetallic alloy can be produced combustion reaction process. On this process, ingredient metal powders are mixed and reacted by combustion. However, powders are fused by reaction heat, and they are difficult to keep the powder condition. There for, we are developed the process to produce intermetallic alloy precursor by slow combustion reaction. On this process, temperature of mixed powders increases slower than 0.2K/sec. while the combustion reaction, and powders are reacted without fusing. Using this process, TiAl presursor is synthesized. Relation of reacting condition and quality of the precursor is evaluated, and researched the practical usage of this precurser.
Fluid inclusion microthermometry was conducted on late‐stage barren comb quartz and the latest stibnite at the Hishikari deposit to characterize the hydrothermal activity responsible for vein ...formation. Eight fluid inclusion assemblages (i.e. fluid inclusions trapped at the same time, ‘FIAs’) were studied to determine the formation fluid temperatures and salinities for the comb quartz in the Shosen No. 2 vein, Sanjin ore zone, and the stibnite in the Seisen No. 1–1 vein, Yamada ore zone.
The average homogenization temperatures (the formation temperatures) of the seven FIAs from the comb quartz were between 207 and 230°C, while the average homogenization temperature (the formation temperature) of an FIA from the stibnite was 113°C. The measured fluid salinities of the seven FIAs from the comb quartz were low, ranging between 0.0 and 1.1 wt% NaCl equiv., indicating that dilute fluids were responsible for the comb quartz formation.
By comparison with previous microthermometric data, the formation temperatures of the studied comb quartz were higher than those of columnar adularia and comb quartz at most other veins (generally around 200°C) but were similar to those of columnar adularia at Keisen veins (230°C) in the same ore zone. The higher formation temperatures both in the Shosen and the Keisen veins in the Sanjin ore zone indicate that the fractures corresponding to the vein system at the Sanjin ore zone were main conduits for hot ascending fluids.
The low formation temperature of stibnite in the latest stage (113°C) indicates that stibnite precipitation occurred during a waning stage of hydrothermal activity. Combined with previous thermodynamic data on antimony solubilities, the large discrepancy between the formation temperature of the comb quartz (200–230°C) and that of the stibnite suggests that the stibnite may have precipitated as a result of a drastic cooling of the hydrothermal system.
Fluid inclusion microthermometry was conducted on late stage comb quartz and the latest stibnite at the Hishikari deposit to characterize the hydrothermal activity responsible for vein formation.
Alumina has high heat resistance and corrosion resistance compared to other ceramics such as silica or mullite. However, for its application to refractory bricks, its high thermal conductivity must ...be reduced. To reduce this thermal conductivity by increasing the porosity, a GS (gelation of slurry) method that can produce high porosity solid foam was applied here to produce the alumina refractory brick. This method was successfully applied to produce alumina foam with high porosity and thermal conductivity of the foam is evaluated. At room temperature, the thermal conductivity was about 0.12W/mK when the foam density was 0.1g/cm3. At elevated temperature above 783K, thermal conductivity of the foam was strongly affected by heat radiation and increased with increasing temperature, in contrast to the thermal conductivity of alumina itself, which decreased with increasing temperature. The alumina foams developed here achieved sufficient thermal insulating properties for use in refractory bricks.
Purpose
Many biliary atresia (BA) patients will eventually develop liver failure even after a successful Kasai portoenterostomy. A common complication of long-term BA survivors with their native ...liver is problematic portal hypertension. The aim of this study was to defend the view that portosystemic shunts can delay or negate the need for transplantation in these children.
Methods
A retrospective single center review of the efficacy of portosystemic shunts in BA patients after a successful Kasai portoenterostomy was conducted.
Results
From 1991 to 2017, 11 patients received portosystemic shunts. Median age of Kasai operation was 48 (36–61) days. Shunts were performed at the median age of 6.2 (4.1–6.8) years. Three of these eleven patients required subsequent liver transplantation. OS at 5 and 10 years were 90.9% and 81.8%, respectively. TFS at 5 and 10 years were 90.9% and 72.7%, respectively. Long-term complications included mild encephalopathy in 2 patients, hypersplenism in 3, and cholestasis in 1.
Conclusion
Portosystemic shunt for the treatment of portal hypertension in carefully selected BA patients is an effective option in delaying or negating the need for liver transplantation.
ABCG2, also known as BCRP, is a high-capacity urate exporter, the dysfunction of which raises gout/hyperuricemia risk. Generally, hyperuricemia has been classified into urate 'overproduction type' ...and/or 'underexcretion type' based solely on renal urate excretion, without considering an extra-renal pathway. Here we show that decreased extra-renal urate excretion caused by ABCG2 dysfunction is a common mechanism of hyperuricemia. Clinical parameters, including urinary urate excretion, are examined in 644 male outpatients with hyperuricemia. Paradoxically, ABCG2 export dysfunction significantly increases urinary urate excretion and risk ratio of urate overproduction. Abcg2-knockout mice show increased serum uric acid levels and renal urate excretion, and decreased intestinal urate excretion. Together with high ABCG2 expression in extra-renal tissues, our data suggest that the 'overproduction type' in the current concept of hyperuricemia be renamed 'renal overload type', which consists of two subtypes-'extra-renal urate underexcretion' and genuine 'urate overproduction'-providing a new concept valuable for the treatment of hyperuricemia and gout.
To investigate melting and solidification behavior during selective laser melting (SLM), the shape of the solidified materials and energy balance during SLM were evaluated through temperature ...measurements with a two-color pyrometer. The laser power and scanning speed were selected as parameters to melt Ti-6Al-4V powder in a square area. The input energy per unit area used during SLM was 5, 10, 16, or 20 J/mm
2
. The melting depth and width increased as the input energy increased. However, the aspect ratio of the melted area was constant. The mass ratio of melted to sintered material decreased as input energy increased. It was considered that the surplus input energy was used for sintering when the energy was high. Color maps show that the surface temperature distribution around the laser irradiation area was asymmetric, in which the temperature gradient at the solidified material side was smoother than that at powder side. The temperature history showed that melting and solidification occurred repeatedly during irradiation.
Although postcapillary pulmonary hypertension (PH) is an important prognostic factor for patients with heart failure (HF), its pathogenesis remains to be fully elucidated. To elucidate the different ...roles of Rho-kinase isoforms, ROCK1 and ROCK2, in cardiomyocytes in response to chronic pressure overload, we performed transverse aortic constriction (TAC) in cardiac-specific ROCK1-deficient (cROCK1
−/−) and ROCK2-deficient (cROCK2
−/−) mice. Cardiomyocyte-specific ROCK1 deficiency promoted pressure-overload-induced cardiac dysfunction and postcapillary PH, whereas cardiomyocyte-specific ROCK2 deficiency showed opposite results. Histological analysis showed that pressure-overload-induced cardiac hypertrophy and fibrosis were enhanced in cROCK1
−/− mice compared with controls, whereas cardiac hypertrophy was attenuated in cROCK2
−/− mice after TAC. Consistently, the levels of oxidative stress were up-regulated in cROCK1
−/− hearts and down-regulated in cROCK2
−/− hearts compared with controls after TAC. Furthermore, cyclophilin A (CyPA) and basigin (Bsg), both of which augment oxidative stress, enhanced cardiac dysfunction and postcapillary PH in cROCK1
−/− mice, whereas their expressions were significantly lower in cROCK2
−/− mice. In clinical studies, plasma levels of CyPA were significantly increased in HF patients and were higher in patients with postcapillary PH compared with those without it. Finally, high-throughput screening demonstrated that celastrol, an antioxidant and antiinflammatory agent, reduced the expressions of CyPA and Bsg in the heart and the lung, ameliorating cardiac dysfunction and postcapillary PH induced by TAC. Thus, by differentially affecting CyPA and Bsg expressions, ROCK1 protects and ROCK2 jeopardizes the heart from pressure-overload HF with postcapillary PH, for which celastrol may be a promising agent.
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