Inhibitory effects of valproic acid in DNA double-strand break repair after irradiation in esophageal squamous carcinoma cells

13301甲第4360号博士(医学)金沢大学博士論文本文Full 以下に掲載:ONCOLOGY REPORTS 34(3) pp.1185-1192 2015. Demetrios A. Spandidos. 共著者:Naoki Makita, Itasu Ninomiya, Tomoya Tsukada, Koichi Okamoto, Shinichi Harada, Shinichi Nakanuma, Seisho Sakai, Isamu Makino, Jun Kinoshita, Hironori Hayashi, Katsunobu Oyama, Hisatoshi Nakagawa, Tomoharu Miyashita, Hidehiro Tajima, Hiroyuki Takamura, Sachio Fushida, Tetsuo Oht

One year of continuous measurements of soil CH4 and CO2 fluxes in a Japanese cypress forest: Temporal and spatial variations associated with Asian monsoon rainfall

We examined the effects of Asian monsoon rainfall on CH[4] absorption of water-unsaturated forest soil. We conducted a 1 year continuous measurement of soil CH[4] and CO[2] fluxes with automated chamber systems in three plots with different soil characteristics and water content to investigate how temporal variations in CH[4] fluxes vary with the soil environment. CH[4] absorption was reduced by the “Baiu” summer rainfall event and peaked during the subsequent hot, dry period. Although CH[4] absorption and CO[2] emission typically increased as soil temperature increased, the temperature dependence of CH[4] varied more than that of CO[2], possibly due to the changing balance of activities between methanotrophs and methanogens occurring over a wide temperature range, which was strongly affected by soil water content. In short time intervals (30 min), the responses of CH[4] and CO[2] fluxes to rainfall were different for each plot. In a dry soil plot with a thick humus layer, both fluxes decreased abruptly at the peak of rainfall intensity. After rainfall, CO[2] emission increased quickly, while CH[4] absorption increased gradually. Release of accumulated CO[2] underground and restriction and recovery of CH[4] and CO[2] exchange between soil and air determined flux responses to rainfall. In a wet soil plot and a dry soil plot with a thinner humus layer, abrupt decreases in CH[4]fluxes were not observed. Consequently, the Asian monsoon rainfall strongly influenced temporal variations in CH[4] fluxes, and the differences in flux responses to environmental factors among plots caused large variability in annual budgets of CH[4] fluxes

Temperature and moisture dependence of daily growth of Scots pine (Pinus sylvestris L.) roots in southern Finland

Scots pine (Pinus sylvestris L.) is one of the most important conifers in northern Europe. In boreal forests, over one-third of net primary production is allocated to roots. Pioneer roots expand the horizontal and vertical root systems and transport nutrients and water from belowground to aboveground. Fibrous roots, often colonized by mycorrhiza, emerge from the pioneer roots and absorb water and nutrients from the soil. In this study, we installed three flatbed scanners to detect the daily growth of both pioneer and fibrous roots of Scots pine during the growing season of 2018, a year with an unexpected summer drought in southern Finland. The growth rate of both types of roots had a positive relationship with temperature. However, the relations between root elongation rate and soil moisture differed significantly between scanners and between root types indicating spatial heterogeneity in soil moisture. The pioneer roots were more tolerance to severe environmental conditions than fibrous roots. The pioneer roots initiated elongation earlier and ceased it later than the fibrous roots. Elongation ended when the temperature dropped below the threshold temperature of 4°C for pioneer roots and 6°C for fibrous roots. During the summer drought, the fibrous roots halted root surface area growth at the beginning of the drought, but there was no drought effect on the pioneer roots over the same period. To compare the timing of root production and the aboveground organs’ production, we used the CASSIA model, which estimates the aboveground tree carbon dynamics. In this study, root growth started and ceased later than growth of aboveground organs. Pioneer roots accounted for 87% of total root productivity. We suggest that future carbon allocation models should separate the roots by root types (pioneer and fibrous), as their growth patterns are different and they have different reactions to changes in the soil environment.Peer reviewe

Short-term effects of biochar on soil CO2 efflux in boreal Scots pine forests

Key message During the first summer, wood biochar amendments increased soil temperature, pH, and soil CO(2)effluxes in a xeric boreal Scots pine forest. The increase of soil CO(2)efflux could be largely explained by increases in by soil temperature. Higher biochar application rates (1.0 vs 0.5 kg m(-2)) led to higher soil CO(2)efflux while the pyrolysis temperature of biochar (500 or 650 degrees C) had no effect on soil CO(2)efflux. Context Using biochar as a soil amendment has been proposed to increase the carbon sequestration in soils. However, a more rapid soil organic matter turnover after biochar application might reduce the effectiveness of biochar applications for carbon sequestration. By raising the pyrolysis temperature, biochar with lower contents of labile carbohydrates can be produced. Aims To better understand the effects of biochar on boreal forest soil, we applied two spruce biochar with different pyrolysis temperatures (500 degrees C and 650 degrees C) at amounts of 1.0 and 0.5 kg m(-2)in a young xeric Scots pine forest in southern Finland. Methods Soil CO2, microbial biomass, and physiochemical properties were measured to track changes after biochar application during the first summer. Results Soil CO(2)increased 14.3% in 1.0 kg m(-2)treatments and 4.6% in 0.5 kg m(-2). Soil temperature and pH were obviously higher in the 1.0 kg m(-2)treatments. Differences in soil CO(2)among treatments disappear after correcting by soil temperature and soil moisture. Conclusion Biochar increased soil CO(2)mainly by raising soil temperature in the short term. Higher biochar application rates led to higher soil CO(2)effluxes. The increase in soil CO(2)efflux may be transient. More studies are needed to get the optimum biochar amount for carbon sequestration in boreal forest.Peer reviewe

Theoretical model for en face optical coherence tomography imaging and its application to volumetric differential contrast imaging

A new formulation of lateral imaging process of point-scanning optical coherence tomography (OCT) and a new differential contrast method designed by using this formulation are presented. The formulation is based on a mathematical sample model called the dispersed scatterer model (DSM), in which the sample is represented as a material with a spatially slowly varying refractive index and randomly distributed scatterers embedded in the material. It is shown that the formulation represents a meaningful OCT image and speckle as two independent mathematical quantities. The new differential contrast method is based on complex signal processing of OCT images, and the physical and numerical imaging processes of this method are jointly formulated using the same theoretical strategy as in the case of OCT. The formula shows that the method provides a spatially differential image of the sample structure. This differential imaging method is validated by measuring in vivo and in vitro samples

Identifying the target genes of SUPPRESSOR OF GAMMA RESPONSE 1, a master transcription factor controlling DNA damage response in Arabidopsis

In mammalian cells, the transcription factor p53 plays a crucial role in transmitting DNA damage signals to maintain genome integrity. However, in plants, orthologous genes for p53 and checkpoint proteins are absent. Instead, the plant-specific transcription factor SUPPRESSOR OF GAMMA RADIATION 1 (SOG1) controls most of the genes induced by gamma irradiation and promotes DNA repair, cell cycle arrest, and stem cell death. Thus far, the genes directly controlled by SOG1 remain largely unknown, limiting the understanding of DNA damage signaling in plants. Here, we conducted a microarray analysis and chromatin immunoprecipitation (ChIP)-sequencing, and identified 146 Arabidopsis genes as direct targets of SOG1. By using the ChIP-sequencing data, we extracted the palindromic motif [CTT(N)7AAG] as a consensus SOG1-binding sequence, which mediates target gene induction in response to DNA damage. Furthermore, DNA damage-triggered phosphorylation of SOG1 is required for efficient binding to SOG1-binding sequence. Comparison between SOG1 and p53 target genes showed that both transcription factors control genes responsible for cell cycle regulation, such as CDK inhibitors, and DNA repair proteins, whereas SOG1 preferentially targets genes involved in homologous recombination. We also found that defense-related genes were enriched in the SOG1 target genes. Consistent with this, SOG1 is required for resistance against the hemi-biotrophic fungus Colletotrichum higginsianum, suggesting that SOG1 has a unique function in controlling immune response. This article is protected by copyright. All rights reserved

A Connexin40 Mutation Associated With a Malignant Variant of Progressive Familial Heart Block Type I

Background-Progressive familial heart block type I (PFHBI) is a hereditary arrhythmia characterized by progressive conduction disturbances in the His-Purkinje system. PFHBI has been linked to genes such as SCN5A that influence cardiac excitability but not to genes that influence cell-to-cell communication. Our goal was to explore whether nucleotide substitutions in genes coding for connexin proteins would associate with clinical cases of PFHBI and if so, to establish a genotype-cell phenotype correlation for that mutation. Methods and Results-We screened 156 probands with PFHBI. In addition to 12 sodium channel mutations, we found a germ line GJA5 (connexin40 [Cx40]) mutation (Q58L) in 1 family. Heterologous expression of Cx40-Q58L in connexin-deficient neuroblastoma cells resulted in marked reduction of junctional conductance (Cx40-wild type [WT], 22.2 ± 1.7 nS, n=14; Cx40-Q58L, 0.56 ± 0.34 nS, n=14; P <0.001) and diffuse localization of immunoreactive proteins in the vicinity of the plasma membrane without formation of gap junctions. Heteromeric cotransfection of Cx40-WT and Cx40-Q58L resulted in homogenous distribution of proteins in the plasma membrane rather than in membrane plaques in ̃ 50% of cells; well-defined gap junctions were observed in other cells. Junctional conductance values correlated with the distribution of gap junction plaques. Conclusions-Mutation Cx40-Q58L impairs gap junction formation at cell-cell interfaces. This is the first demonstration of a germ line mutation in a connexin gene that associates with inherited ventricular arrhythmias and emphasizes the importance of Cx40 in normal propagation in the specialized conduction system

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie