Comparison of east and west chlorophyll a standing stock and oceanic habitat along the Transition Domain of the North Pacific

Chlorophyll (Chl) a was measured every 10 m from 0 to 150 min the Transition Domain (TD), located between 37 and 45°N,and from 160°E to 160°W, in May and June (Leg 1) andin June and July (Leg 2), 1993–96. Total Chl a standingstocks integrated from 0 to 150 m were mostly within the rangeof 20 and 50 mg m^–2. High standing stocks (>50 mg m^–2)were generally observed westof 180°, with the exceptionof the sporadic high values at the easternmost station. Thetotal Chl a standing stock tended to be higher in the westernTD (160°E–172°30'E) than in the central (175°E–175°W)and eastern (170°W–160°W) TD on Leg 1, but thesame result was not observed on Leg 2. It was likely that largephytoplankton (2–10 and >10 µm fractions) contributedto the high total Chl a standing stock. We suggest that thehigh total Chl a standing stock on Leg 1, in late spring andearly summer, reflects the contribution of the spring bloomin the subarctic region of the northwestern Pacific Ocean. Thedistribution of total Chl a standing stock on Leg 2 was scarcelyaffected by the spring phytoplankton bloom, suggesting thattotal Chl a standing stock is basically nearly uniform in theTD in spring and summer. Moreover, year-to-year variation inthe total Chl a standing stock was observed in the western TDon Leg 1, suggesting that phytoplankton productivity and/orthe timing of the main period of the bloom exhibits interannualvariations.     

Inhibition of catalase activity by oxidative stress and its relationship to salicylic acid accumulation in plants

The decrease in catalase activity and its relationship to change in salicylic acid content were investigated in rice, wheat, and cucumber seedlings exposed to oxidative stresses. A decrease in chlorophyll fluorescence (F/Fm), measured as an indicator of the oxidative stress, and a drop in catalase activity were observed following treatment with NaCl in all plant seedlings tested . Furthermore, such decreases in F/Fm and catalase activity were also observed under low temperature conditions in both rice cultivars, whereas the degrees of decrease were dependent on their low temperature tolerance . Although the content of salicylic acid increased in rice seedlings stressed by NaCl treatment, it was inversely correlated with the decrease in the catalase activity . Such a relationship between the decrease in catalase activity and increase in salicylic acid content was confirmed with paraquat treatment of the rice seedlings . These results suggested that the fall in catalase activity is a phenomenon occurring in many plant species under oxidative stress and is related to the accumulation of salicylic acid in oxidatively-stressed plants.     

KIR,HLA, and IL28B Variant Predict Response to Antiviral Therapy in Genotype 1 Chronic Hepatitis C Patients in Japan

Natural killer cell responses play a crucial role in virus clearance by the innate immune system. Although the killer immunoglobulin-like receptor (KIR) in combination with its cognate human leukocyte antigen (HLA) ligand, especially KIR2DL3-HLA-C1, is associated with both treatment-induced and spontaneous clearance of hepatitis C virus (HCV) infection in Caucasians, these innate immunity genes have not been fully clarified in Japanese patients. We therefore investigated 16 KIR genotypes along with HLA-B and -C ligands and a genetic variant of interleukin (IL) 28B (rs8099917) in 115 chronic hepatitis C genotype 1 patients who underwent pegylated-interferon-α2b (PEG-IFN) and ribavirin therapy. HLA-Bw4 was significantly associated with a sustained virological response (SVR) to treatment (P = 0.017; odds ratio [OR] = 2.50, ), as was the centromeric A/A haplotype of KIR (P = 0.015; OR 3.37). In contrast, SVR rates were significantly decreased in patients with KIR2DL2 or KIR2DS2 (P = 0.015; OR = 0.30, and P = 0.025; OR = 0.32, respectively). Multivariate logistic regression analysis subsequently identified the IL28B TT genotype (P = 0.00009; OR = 6.87, 95% confidence interval [CI] = 2.62 - 18.01), KIR2DL2/HLA-C1 (P = 0.014; OR = 0.24, 95% CI = 0.08 - 0.75), KIR3DL1/HLA-Bw4 (P = 0.008, OR = 3.32, 95% CI = 1.37 - 8.05), and white blood cell count at baseline (P = 0.009; OR = 3.32, 95% CI = 1.35 - 8.16) as independent predictive factors of an SVR. We observed a significant association between the combination of IL28B TT genotype and KIR3DL1-HLA-Bw4 in responders (P = 0.0019), whereas IL28B TT along with KIR2DL2-HLA-C1 was related to a non-response (P = 0.0067). In conclusion, combinations of KIR3DL1/HLA-Bw4, KIR2DL2/HLA-C1, and a genetic variant of the IL28B gene are predictive of the response to PEG-IFN and ribavirin therapy in Japanese patients infected with genotype 1b HCV.     

Cell-to-cell interaction analysis of prognostic ligand-receptor pairs in human pancreatic ductal adenocarcinoma

Cell-to-cell interactions (CCIs) through ligand-receptor (LR) pairs in the tumor microenvironment underlie the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). However, there is scant knowledge of the association of CCIs with PDAC prognosis, which is critical to the identification of potential therapeutic candidates. Here, we sought to identify the LR pairs associated with PDAC patient prognosis by integrating survival analysis and single-cell CCI prediction. Via survival analysis using gene expression from cancer cohorts, we found 199 prognostic LR pairs. CCI prediction based on single-cell RNA-seq data revealed the enriched LR pairs associated with poor prognosis. Notably, the CCIs involved epithelial tumor cells, cancer-associated fibroblasts, and tumor-associated macrophages through integrin-related and ANXA1–FPR pairs. Finally, we determined that CCIs involving 33 poor-prognostic LR pairs were associated with tumor grade. Although the clinical implication of the set of LR pairs must be determined, our results may provide potential therapeutic targets in PDAC.     

Intracoronary artery transplantation of cardiomyoblast-like cells from human adipose tissue-derived multi-lineage progenitor cells improve left ventricular dysfunction and survival in a swine model of chronic myocardial infarction

Transplantation of human cardiomyoblast-like cells (hCLCs) from human adipose tissue-derived multi-lineage progenitor cells improved left ventricular function and survival of rats with myocardial infarction. Here we examined the effect of intracoronary artery transplantation of human CLCs in a swine model of chronic heart failure. Twenty-four pigs underwent balloon-occlusion of the first diagonal branch followed by reperfusion, with a second balloon-occlusion of the left ascending coronary artery 1week later followed by reperfusion. Four weeks after the second occlusion/reperfusion, 17 of the 18 surviving animals with severe chronic MI (ejection fraction <35% by echocardiography) were immunosuppressed then randomly assigned to receive either intracoronary artery transplantation of hCLCs hADMPCs or placebo lactic Ringer's solution with heparin. Intracoronary artery transplantation was followed by the distribution of DiI-stained hCLCs into the scarred myocardial milieu. Echocardiography at post-transplant days 4 and 8weeks showed rescue and maintenance of cardiac function in the hCLCs transplanted group, but not in the control animals, indicating myocardial functional recovery by hCLCs intracoronary transplantation. At 8week post-transplantation, 7 of 8 hCLCs transplanted animals were still alive compared with only 1 of the 5 control (p=0.0147). Histological studies at week 12 post-transplantation demonstrated engraftment of the pre DiI-stained hCLCs into the scarred myocardium and their expression of human specific alpha-cardiac actin. Human alpha cardiac actin-positive cells also expressed cardiac nuclear factors; nkx2.5 and GATA-4. Our results suggest that intracoronary artery transplantation of hCLCs is a potentially effective therapeutic strategy for future cardiac tissue regeneration.     

Mechanistic studies on the intramolecular one-electron transfer between the two flavins in the human endothelial NOS reductase domain

The object of this study was to clarify the mechanism of electron transfer in the human endothelial nitric oxide synthase (eNOS) reductase domain using recombinant eNOS reductase domains; the FAD/NADPH domain containing FAD- and NADPH-binding sites and the FAD/FMN domain containing FAD/NADPH-, FMN-, and a calmodulin-binding sites. In the presence of molecular oxygen or menadione, the reduced FAD/NADPH domain is oxidized via the neutral (blue) semiquinone (FADH(*)), which has a characteristic absorption peak at 520 nm. The FAD/NADPH and FAD/FMN domains have high activity for ferricyanide, but the FAD/FMN domain has low activity for cytochrome c. In the presence or absence of calcium/calmodulin (Ca(2+)/CaM), reduction of the oxidized flavins (FAD-FMN) and air-stable semiquinone (FAD-FMNH(*)) with NADPH occurred in at least two phases in the absorbance change at 457nm. In the presence of Ca(2+)/CaM, the reduction rate of both phases was significantly increased. In contrast, an absorbance change at 596nm gradually increased in two phases, but the rate of the fast phase was decreased by approximately 50% of that in the presence of Ca(2+)/CaM. The air-stable semiquinone form was rapidly reduced by NADPH, but a significant absorbance change at 520 nm was not observed. These findings indicate that the conversion of FADH(2)-FMNH(*) to FADH(*)-FMNH(2) is unfavorable. Reduction of the FAD moiety is activated by CaM, but the formation rate of the active intermediate, FADH(*)-FMNH(2) is extremely low. These events could cause a lowering of enzyme activity in the catalytic cycle.     

Association between serum calcium and periodontal disease progression in non-institutionalized elderly

Objective: To assess the effect of baseline serum calcium on the progression of periodontal disease in non‐institutionalized elderly. Background: Although a few studies have found some evidence of the role played by dietary calcium in periodontal disease process, there is a paucity of information pertinent to longitudinal assessment of serum calcium‐periodontal relationships. Material and methods: Clinical attachment levels of 266 Japanese subjects aged 70 years were recorded at baseline and annually for six consecutive years. Progression of periodontal disease (PPD) was defined as the number of teeth that showed additional attachment loss of ≥3 mm during the 6 years. The number of PPD was calculated for each subject and categorised into four levels, namely, PPD₀, PPD₁, PPD₂ and PPD₃ where the number of teeth with additional attachment loss ranged from 0, 1–10, 11–20 and >20 respectively. The levels of serum calcium, albumin, random blood sugar, immunoglobulin (IgG, IgA and IgM), gender, smoking habits, education, gingival bleeding and the number of teeth present were obtained at baseline. Results: Serum calcium, IgA, smoking, gingival bleeding and teeth present were associated with PPD at p ≤ 0.10 and were included in a multinomial logistic regression analysis. Serum calcium was the only variable that was significantly associated with PPD with relative risks of 100 at PPD₁ and PPD₂, respectively, and 1000 at PPD₃. Conclusion: Serum calcium may be considered a risk factor for periodontal disease progression in non‐institutionalized elderly.     

Correlation of neutrophil and monocyte derived interleukin-1 receptor antagonist and interleukin-8 with colitis severity in the rabbit

Activated neutrophils and monocytes produce interleukin (IL)-8, a pro-inflammatory chemokine, but also IL-1 receptor antagonist (IL-1ra), which is an anti-inflammatory cytokine. We were interested to see the profiles of IL-8 and IL-1ra in the colonic tissue and in the peripheral blood leukocytes (PBL) during the development of immune complex induced colitis in rabbits. IL-1ra and IL-8 in PBL were measured in 26 rabbits at time 0 h, 24 h, and 48 h after induction of colitis. The colons were removed at 48 h for measuring myeloperoxidase (MPO), ulcer area, IL-1ra and IL-8. Epithelial damage, crypt abscess formation and leukocyte infiltration of the colonic tissue were major features of this colitis model. During the development of colitis, there was an increase in circulating neutrophils and monocytes (P < 0.0001), but not lymphocytes. Likewise, elevated amounts of IL-1ra (P = 0.0001) and IL-8 (P = 0.0219) production by PBL were observed following induction of colitis. Flow cytometry revealed major source of IL-1ra was monocytes, while the main sources of IL-8 were neutrophils and monocytes. There was correlation between MPO and ulcer area (R_s = 0.6327, P < 0.0001). At 24 h, PBL from MPO^High group (n = 11) showed increased IL-1ra (P = 0.027) and IL-8 (P = 0.0128) levels vs MPO^Low group (n = 15). IL-8 production by PBL showed correlation with tissue MPO (R_s = 0.4273, P = 0.0295). The colitis in this model was associated with an increase in circulating monocytes and neutrophils, which released increased amounts of IL-8 and IL-1ra. Further, IL-8 and IL-1ra showed correlation with the severity of colitis. These observations should significantly further understandings on the role of neutrophils and monocytes in the immunopathogenesis of ulcerative colitis.