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Obesity and diabetes are independent risk factors for death during sepsis. S100A8, an alarmin, is related to inflammation, obesity, and diabetes. Here, we examine the role of S100A8 in sepsis of obesity and diabetes models. Injection of S100A8 prolongs the survival of septic mice induced by lethal endotoxemia

Uncoupling protein 2 (UCP2), a mitochondrial protein, is known to be upregulated in pancreatic islets of patients with type 2 diabetes (T2DM); however, the pathological significance of this increase in UCP2 expression is unclear. In this study, we highlight the molecular link between the increase in UCP2 expression in β-cells and β-cell failure by using genetically engineered mice and human islets. β-cell-specific UCP2-overexpressing transgenic mice (βUCP2Tg) exhibited glucose intolerance and a reduction in insulin secretion. Decreased mitochondrial function and increased aldolase B (AldB) expression through oxidative-stress-mediated pathway were observed in βUCP2Tg islets. AldB, a glycolytic enzyme, was associated with reduced insulin secretion via mitochondrial dysfunction and impaired calcium release from the endoplasmic reticulum (ER). Taken together, our findings provide a new mechanism of β-cell dysfunction by UCP2 and AldB. Targeting the UCP2/AldB axis is a promising approach for the recovery of β-cell function.

Plant activators such as benzothiadiazole (BTH) protect plants against diseases by priming the salicylic acid (SA) signaling pathway. In rice, the transcription factor WRKY45 plays a central role in this process. To investigate the mechanism involved in defense-priming by BTH and the role of WRKY45 in this process, we analyzed the transcripts of biosynthetic genes for diterpenoid phytoalexins (DPs) during the rice–Magnaporthe oryzae interaction. The DP biosynthetic genes were barely upregulated in BTH-treated rice plants, but were induced rapidly after M. oryzae infection in a WRKY45-dependent manner. These results indicate that the DP biosynthetic genes were primed by BTH through WRKY45. Rapid induction of the DP biosynthetic genes was also observed after M. oryzae infection to WRKY45-overexpressing (WRKY45-ox) plants. The changes in gene transcription resulted in accumulation of DPs in WRKY45-ox and BTH-pretreated rice after M. oryzae infection. Previously, we reported that cytokinins (CKs), especially isopentenyladenines, accumulated in M. oryzae-infected rice. Here, we show that DP biosynthetic genes are regulated by the SA/CK synergism in a WRKY45-dependent manner. Together, we propose that CK plays a role in mediating the signal of M. oryzae infection to trigger the induction of DP biosynthetic genes in BTH-primed plants. Electronic supplementary material The online version of this article (doi:10.1007/s11103-014-0221-x) contains supplementary material, which is available to authorized users.

Rice (Oryza sativa) produces diterpenoid phytoalexins (DPs), momilactones and phytocassanes as major phytoalexins. Accumulation of DPs is induced in rice by blast fungus infection, copper chloride or UV light. Here, we describe a rice transcription factor named diterpenoid phytoalexin factor (DPF), which is a basic helix-loop-helix (bHLH) transcription factor. The gene encoding DPF is expressed mainly in roots and panicles, and is inducible in leaves by blast infection, copper chloride or UV. Expression of all DP biosynthetic genes and accumulation of momilactones and phytocassanes were remarkably increased and decreased in DPF over-expressing and DPF knockdown rice, respectively. These results clearly demonstrated that DPF positively regulates DP accumulation via transcriptional regulation of DP biosynthetic genes, and plays a central role in the biosynthesis of DPs in rice. Furthermore, DPF activated the promoters of COPALYL DIPHOSPHATE SYNTHASE2 (CPS2) and CYTOCHROME P450 MONOOXYGENASE 99A2 (CYP99A2), whose products are implicated in the biosynthesis of phytocassanes and momilactones, respectively. Mutations in the N-boxes in the CPS2 upstream region, to which several animal bHLH transcription factors bind, decreased CPS2 transcription, indicating that DPF positively regulates CPS2 transcription through the N-boxes. In addition, DPF partly regulates CYP99A2 through the N-box. This study demonstrates that DPF acts as a master transcription factor in DP biosynthesis.

The EPF family of plant TFIIIA-type zinc-finger (ZF) proteins (ZPTs) is characterized by long linkers separating ZF motifs. We previously reported that two-fingered ZPTs bind to two tandem core sites that are separated by several base pairs, each ZF making contact with one core site. Here we report further characterization of DNA-binding activities of ZPTs using four family members, ZPT2-14, ZPT2-7, ZPT2-8, and ZPT2-2, having inter-ZF linkers of different lengths and sequences, to investigate the correlation of the length and/or sequence of the linker with preference for the spacing between core sites in target DNAs. Selected and amplified binding site (SAAB)-imprinting assays and gel mobility shift assays prompted three conclusions. (1) The four ZPTs have common specificity for core binding sites—two AGT(G)/(C)ACTs separated by several nucleotides. (2) The four ZPTs prefer a spacing of 10 bases between the core sites, but each ZPT has its own preference for suboptimal spacing. (3) At a particular spacing, two zinc fingers may bind to the core sites on both strands. The results provide new information about how the diversity in linker length/sequence affects DNA-sequence recognition in this protein family.

Differences in serum lipids, apoprotein levels, and fatty acid compositions were investigated in normal and hyperlipidemic female subjects in a rural area of Japan. Compared with normolipidemic subjects, hyperlipidemic ones of type IIa showed only slight differences in fatty acid composition in the cholesterol ester fraction. Also compared with normolipidemic subjects, the type IIb group had a lower proportion of 18:2 fatty acids in the phospholipid fraction, while 16:1 and 18:1 fatty acids were higher and 18:2 fatty acids were lower in the cholesterol ester fraction. Regarding type IV hyperlipidemics vs. normolipidemics, differences were evident in that in the former percentages of 18:2 fatty acids were lower in the cholesterol ester, phospholipid, and triglyceride fractions, while the percentages of 16:0 fatty acids were higher in the cholesterol ester and triglyceride fractions and that of 22:6 fatty acid in the phospholipid fraction was higher. Dietary fatty acid composition and cholesterol intake did not differ significantly among the groups.

A class-C floral homeotic gene of Petunia , pMADS3 , is specifically expressed in the stamen and carpels of developing flowers. We had previously reported the ect- pMADS3 phenomenon in which introduction of a part of the pMADS3 genomic sequence, including intron 2, induces ectopic expression of endogenous pMADS3 . Unlike transcriptional or posttranscriptional gene silencing triggered by the introduction of homologous sequences, this observation is unique in that the gene expression is up-regulated. In this study, we demonstrated that the ect- pMADS3 phenomenon is due to transcriptional activation based on RNA-directed DNA methylation (RdDM) occurring in a particular CG in a putative cis -element in pMADS3 intron 2. The CG methylation was maintained over generations, along with pMADS3 ectopic expression, even in the absence of RNA triggers. These results demonstrate a previously undescribed transcriptional regulatory mechanism that could lead to the generation of a transcriptionally active epiallele, thereby contributing to plant evolution. Our results also reveal a putative negative cis -element for organ-specific transcriptional regulation of class-C floral homeotic genes, which could be difficult to identify by other approaches.

The relationship between habitual milk intake and levels of serum lipids and their apoproteins, serum cholesterol, and triglycerides and their apoproteins was investigated in 119 male inhabitants in a rural coastal area in Japan. Subjects were divided into three groups according to their daily milk intake, i.e., small (S) (0-60ml/day), medium (M) (61-200ml/day), and large intake (L)(over 200ml/day). Among the normolipidemic subjects, the obesity index in the L group was higher than that in the S group. Total cholesterol, LDL-cholesterol, and apoB concentrations were also significantly higher in the L group than in the S and M groups. In the hypercholesterolemia group, obesity index, total cholesterol, triglyceride, and apoE tended to be higher; and apoA-I and apoB were lower in the L group than in the S group. The subjects in the L group of hypercholesterolemia tended to take in more confectionery, more fish, less vegetables, and less fungi as compared with those in the S group. As a result, the subjects with daily habitual milk intake appear to consume foods that promote obesity, such as those popular in the United States of America and Europe, especially the subjects in the hypercholesterolemia group. The quality and quantity of foods with 200ml of daily milk intake should be selected carefully for hypercholesterolemic Japanese.

ZPT2-2 is a DNA-binding protein of petunia that contains two canonical TFIIIA-type zinc finger motifs separated by a long linker. We previously reported that ZPT2-2 bound to two separate AGT core sites, with each zinc finger making contact with each core site. Here we present our further characterization of ZPT2-2 by using selected and amplified binding sequence imprinting and surface plasmon resonance analyses; together, these assays revealed some unusual features of the interaction between ZPT2-2 and DNA. These experiments allowed us to conclude that 1) the optimal binding sequence for the N-terminal zinc finger is AGC(T), and that of the C-terminal one is CAGT; 2) multiple arrangements of the two core sites accommodate binding; and 3) the spacing between the two core sites affects the binding affinity. In light of these observations, we propose a new model for the DNA-ZPT2-2 interaction. Further, consistent with this model, a high affinity binding site for ZPT2-2 was found in the promoter region of the ZPT2-2 gene. This site may serve as a cis-element for the autoregulation of ZPT2-2 gene expression.

Subjects The subjects were 126 male and 205 female healthy inhabitants aged between 30 and 72 years, who were living in Kisei-cho, Mie Prefecture, a rural area located in the middle of Japan. They attended the annual cardiovascular health check between the years of 1985 and 1989. We examined the blood flow of the common carotid arteries by the QFM 2OOOXA, and also the body mass index (kg/m2), blood pressure, serum lipids, hematocrit (Ht) and platelet aggregation after the overnight fast. Obesity was defined as 25 kg/m2 and more of BMI. QFM (the ultrasonic quantitative flow measurement system) consists of two systems: one is for measuring the vessel diameter (D) and its deviation ranges (dD) by the ultrasonic echo tracking (6 MHz); and the other is for measuring the absolute blood velocity by a doppler method (5 MHz) independent of the beam angles with a one-transmittertwo-receivers system [ 1,2]. The blood volume is computed from a vessel cross sectional area and the blood velocity. The volume elastic modulus (VP) was obtained by the formula VE = (Ps - Pd) x D/2dD. The circulation resistance (Zo) on the region from the common carotid artery to the cerebral artery is calculated.

減塩食事指導時における“うす味”評価の客観性を高め, 指導効果を上げることを目的として, 食塩味覚閾値判定用濾紙を考案・作製し, 健常者, 三重県内の一般住民, 病院において減塩食事療法を行った者につき, 味覚検査を行った。塩味の知覚閾値は, 健常者に比べて, 一般住民群と病院患者群で有意に高かった。入院治療前に比べて後では, 男女とも知覚閾値が低下しており, 食事療法により食塩に対する感度が高まり,“うす味”を識別する能力が獲得されたことが示された。食塩感度テストを減塩食事療法における栄養指導時に用いることは, 指導効果を上げるために有効と思われた。