HNF1A Mutations and Beta Cell Dysfunction in Diabetes

Understanding the genetic factors of diabetes is essential for addressing the global increase in type 2 diabetes. HNF1A mutations cause a monogenic form of diabetes called maturity-onset diabetes of the young (MODY), and HNF1A single-nucleotide polymorphisms are associated with the development of type 2 diabetes. Numerous studies have been conducted, mainly using genetically modified mice, to explore the molecular basis for the development of diabetes caused by HNF1A mutations, and to reveal the roles of HNF1A in multiple organs, including insulin secretion from pancreatic beta cells, lipid metabolism and protein synthesis in the liver, and urinary glucose reabsorption in the kidneys. Recent studies using human stem cells that mimic MODY have provided new insights into beta cell dysfunction. In this article, we discuss the involvement of HNF1A in beta cell dysfunction by reviewing previous studies using genetically modified mice and recent findings in human stem cell-derived beta cells.     

Accelerator-driven system for transmutation of high-level waste

The accelerator-driven transmutation system has been studied at the Japan Atomic Energy Research Institute. This system is a hydrid system which consists of a high intensity accelerator, a spallation target and a subcritical core region. In the conceptual design study, two types of system concepts, sodium cooled and lead-bismuth cooled system, are being studied. In this study, we fucus on our lead-bismuth cooled accelerator-driven transmutation system to investigate basic characteristics. The fuel compositions were optimized for efficient transmutation of minor actinide. The transmutation of long-lived fission products was also considered.     

Crystalline Sodium Selenocarboxylates – synthesis and characterization

A series of sodium selenocarboxylates 2 were isolated from the reaction of diacyl selenides with sodium ethanolate and characterized. A convenient preparation of the sodium salts 2 by the direct reaction of acyl chlorides with sodium selenide was also established. The salts are colourless to slightly pale yellow crystals and labile towards moisture. They readily react with alkyl iodides at room temperature to give the corresponding Se-alkyl esters 3 .     

Analysis of Plasmalogen Species in Foodstuffs

Ethanolamine plasmalogen (PlsEtn), which is present at high levels in brains, is believed to be involved in neuronal protection. The present study was performed to search for PlsEtn resources in foodstuffs. The foodstuffs examined showed a wide range of PlsEtn contents from 5 to 549 μmol/100 g wet wt. The marine invertebrates, blue mussel, and ascidian had high PlsEtn contents (over 200 μmol/100 g wet wt). Profiling of the molecular species showed that the predominant fatty acids of PlsEtn species were 20:5 (EPA) and 22:6 (DHA) at the sn‐2 position of the glycerol moiety in marine foodstuffs, whereas major PlsEtn species in land foodstuffs were 20:4. Following quantitative analysis by multiple reaction monitoring, the ascidian viscera were shown to contain the highest levels of 18:0/20:5‐PlsEtn and 18:0/22:6‐PlsEtn (86 and 68 μmol/100 g wet wt, respectively). In order to evaluate a neuronal antiapoptotic effect of these PlsEtn species, human neuroblastoma SH‐SY5Y cells were treated with ethanolamine glycerophospholipid (EtnGpl), purified from the ascidian viscera, under serum starvation conditions. Extrinsic EtnGpl from ascidian viscera showed stronger suppression of cell death induced by serum starvation than with bovine brain EtnGpl. The EtnGpl from ascidian viscera strongly suppressed the activation of caspase 3. These results suggest that PlsEtn, especially that containing EPA and DHA, from marine foodstuffs is potentially useful for a therapeutic dietary supplement preventing neurodegenerative diseases, such as Alzheimer's disease (AD).     

Vitamin E reduces cholesterol esterification and uptake of acetylated low density lipoprotein in macrophages

The effects of vitamin E on cholesteryl ester (CE) metabolism in 1774 cells were examined. Pretreatment of 1774 cells with vitamin E at concentrations above 50 μM significantly decreased acetylated low density lipoprotein (LDL)-induced incorporation of [¹⁴C]oleate into CF in cells in a dose-dependent manner. This was partly due to vitamin E Also significantly inhibiting the uptake of [³H]CE-labeled acetylated LDL by 1774 cells. A trend existed toward suppression of acyl-CoA:cholesterol acyltransferase (ACAT) activity in the cell lysate at high vitamin E concentration, but there was no effect on hydrolysis of CE. These data indicate that vitamin E reduces the uptake of modified LDL and suppresses ACAT activity, resulting in less cholesterol esterification in macrophages; a novel mechanism underlying the antiatherogenic properties of vitamin E.     

Distributions of hydroperoxide positional isomers generated by oxidation of 1-palmitoyl-2-arachidonoyl-<Emphasis Type="Italic">sn</Emphasis>-glycero-3-phosphocholine in liposomes and in methanol solution

The differences in distribution of geometric isomers of unsaturated PC hydroperoxides generated by free radical oxidation were compared, as corresponding hydroxy analogs, in heterogeneous liposomes and in a homogeneous methanol solution by using HPLC with UV detection due to the presence of conjugated dienes. Identification of fractionated peak components was carried out by GC-MS. When the oxidation of 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine, PC(16∶0/18∶2), was initiated in liposomes by a hydrophilic azo radical initiator, and in a methanol solution by a hydrophobic azo radical initiator, there was no significant difference in the relative percentages of 1-palmitoyl-2-(9-hydroxy-trans-10,trans-12-octadecadienoyl)-sn-glycero-3-phosphocholine (9-t,t-OH PC) and 1-palmitoyl-2-(13-hydroxy-trans-9,trans-11-octadecadienoyl)-sn-glycero-3-phosphocholine (13-t,t-OH PC) between the PC oxidized in liposomes and in the methanol solution. For the oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, PC(16∶0/20∶4), the relative percentage of 1-palmitoyl-2-(5-hydroxy-trans-6,cis-8,11,14-eicosatetraenoyl)-sn-glycero-3-phosphocholine (5-OH PC) was significantly higher (P<0.01) than that of 1-palmitoyl-2-(15-hydroxy-cis-5,8,11,trans-13-eicosatetraenoyl)-sn-glycero-3-phosphocholine (15-OH PC) in liposomes. For the homogeneous methanol solution of PC(16∶0/20∶4), the relative percentage of 5-OH PC was close to that of 15-OH PC. For the PC(16∶0/20∶4) oxidized in bulk with added pentamethylchromanol, the individual amount of 15-OH PC, 1-palmitoyl-2-(11-hydroxy-cis-5,8trans-12,cis-14-eicosatetraenoyl)-sn-glycero-3-phosphocholine (11-OH PC), 1-palmitoyl-2-(12-hydroxy-cis-5,8,trans-10,cis-14-eicosatetraenoyl)-sn-glycero-3-phosphocholine (12-OH PC), 1-palmitoyl-2-(8-hydroxy-cis-5,trans-9,cis-11,14-eicosatetraenoyl)-sn-glycero-3-phosphocholine (8-OH PC), 1-palmitoyl-2-(9-hydroxy-cis-5,trans-7,cis-11,14-eicosatetraenoyl)-sn-glycero-3-phosphocholine (9-OH PC), and 5-OH PC were close to each other compared to the corresponding values in liposomes and in methanol solution. The results obtained by gel permeation chromatography of the PC liposomes containing hydrophilic 2,2′-azobis-2-amidinopropane) dihydrochloride (AAPH) suggest that the AAPH added to the liposomes of PC(16∶0/20∶4) was partitioned into the water phase and out of the hydrophobic region of the fatty acyl moieties of the PC. These results confirm that the distance that exists in the bis-allylic carbons of the unsaturated fatty acyl moieties of PC from the interface between the hydrophilic region of PC and the water phases played an important role in influencing hydrogen abstraction to form a symmetrical distribution of hydroperoxide isomers in both the heterogeneous liposomes and the homogeneous methanol solution.     

Push-Pull Fatigue of Sintered Silicon Nitride Ceramics at Elevated Temperatures

The fatigue tests under push-pull completely reversed loading and pulsating loading were performed for silicon nitride ceramics at elevated temperatures. Then the effects of stress wave form, stress rate, and cyclic understressing on fatigue strength, and cyclic straining behavior, were examined. The cycle-number-based fatigue life is found to be shorter under trapezoidal stress wave loading than under triangular stress wave loading, and to become shorter with increasing hold time under the trapezoidal stress wave loading. Meanwhile, the equivalent time-based life curve, which is estimated from the concept of slow crack growth, almost agrees with the static fatigue life curve in the short and intermediate life regions, showing the small cyclic stress effect and the dominant stress-imposing period effect on cyclic fatigue life. The fatigue strength increased in stepwise stress amplitude increasing test, where stress amplitude is increased stepwise every given number of stress cycles, at 1100° and 1200°C. Occurrence of cyclic strengthening was proved through a gradual decrease in strain amplitude during a pulsating loading test at 1200°C in this material, corresponding to the above cyclic understressing effect on fatigue strength.     

Formation Processes of β-C2S by the Decomposition of Hydrothermally Prepared C-S-H with Ca(OH)2

A mixture of CaO and silicic acid prepared with a Ca/Si ratio of 2.0 was hydrothermally synthesized at 80° to 200°C, and the thermal decomposition behavior of the products (C-S-H with Ca(OH)₂) was analyzed using XRD, ²⁹Si MAS NMR, and the trimethylsililation method (TMS). It was found that the main silicate anion structure of C-S-H was a mixture of a dimer and a single-chain polymer (larger than Si₅O₁₆) and that polymerization advanced with an increase of the synthesizing temperature. On heating, the products decomposed to form β-C₂S. It was found that the decomposition was gradual and that the-higher the temperature of hydrothermal synthesis, the lower was the temperature of the decomposition into β-C₂S. Although the decomposition proceeded to form a monomer (β-C₂S) from the polymer and dimer, this dimer was resistant to heat and did not decompose unless heated to above 400°C.     

Liver phosphatidylcholine hydroperoxidation provoked by ethionine-containing choline-deficient diet in mice

It is shown that peroxidation of phosphatidylcholine (PC) is enhanced in liver of mice fed a hepatocarcinogenic choline-deficient diet containing 0.1% w/w ethionine. Mice were divided into 4 groups and fed for 3 weeks one of the following diets: choline-supplemented; choline-supplemented containing ethionine; choline-deficient; and choline-deficient containing ethionine. Phosphatidylcholine hydroperoxide (PCOOH) of liver lipids was measured by high performance liquid chromatography using a chemiluminescence detector. Mice fed a choline-deficient diet containing ethionine showed 6-fold higher PCOOH levels than the choline-supplemented control mice: the PCOOH/PC molar ratios of liver lipids were 32.3×10⁻⁵ and 5.6×10⁻⁵, respectively. In addition to this remarkable degree of lipid peroxidation in liver of mice fed the choline-deficient diet containing ethionine, we also observed a significant liver fatty infiltration, a decrease in plasma and liver α-tocopherol, and an increase in liver injury-indicative enzyme activities. Also, marker enzymes for hepatocarcinogenesis, glucose-6-phosphatase and γ-glutamyl transpeptidase were affected. These data suggest that enhanced hydroperoxidation of phosphatidylcholine may participate in hepatocarcinogenesis provoked by choline deficiency in the presence of ethionine.     

Effect of steric hindrance on hydrogen‐bonding interaction between polyesters and natural polyphenol catechin

The phase behaviors for the blends of poly(3‐hydroxypropionate) (PHP), poly(L ‐lactide) (PLLA), poly(D ‐lactide) (PDLA), and poly(D,L ‐lactide) (PDLLA) with catechin were investigated by differential scanning calorimetry. In PLLA/catechin, PDLA/catechin, and PDLLA/catechin blends, two glass transitions were detected when the catechin content was ≥40 wt %, whereas in PHP/catechin blends only one glass transition was observed over the whole range of blend compositions. The former and the latter results should reflect the inhomogeneous and the homogeneous nature of the blends, respectively, in the amorphous phase. These different phase behaviors should arise from the differences in the chemical structures between PHP and PLLA/PDLA/PDLLA, which dominates the strength and the number of intermolecular hydrogen‐bonding interactions between the ester carbonyl groups of polyesters and the phenol groups of catechin. As detected by FTIR spectroscopy, in comparison with PHP, the steric hindrance of side‐chain methyl groups of PLLA, PDLA, and PDLLA might restrain the formation of hydrogen bonds between their ester carbonyl groups and the phenol hydroxyl groups of catechin, even weakening the strength of such hydrogen bonds. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 91: 3565–3573, 2004