BH3-only Protein Noxa Is a Mediator of Hypoxic Cell Death Induced by Hypoxia-inducible Factor 1α

Hypoxia is a common cause of cell death and is implicated in many disease processes including stroke and chronic degenerative disorders. In response to hypoxia, cells express a variety of genes, which allow adaptation to altered metabolic demands, decreased oxygen demands, and the removal of irreversibly damaged cells. Using polymerase chain reaction–based suppression subtractive hybridization to find genes that are differentially expressed in hypoxia, we identified the BH3-only Bcl-2 family protein Noxa. Noxa is a candidate molecule mediating p53-induced apoptosis. We show that Noxa promoter responds directly to hypoxia via hypoxia-inducible factor (HIF)-1α. Suppression of Noxa expression by antisense oligonucleotides rescued cells from hypoxia-induced cell death and decreased infarction volumes in an animal model of ischemia. Further, we show that reactive oxygen species and resultant cytochrome c release participate in Noxa-mediated hypoxic cell death. Altogether, our results show that Noxa is induced by HIF-1α and mediates hypoxic cell death

Reinforcing effects of methamphetamine in an animal model of Attention-Deficit/Hyperactivity Disorder-the Spontaneously Hypertensive Rat

Substrains of the Spontaneously Hypertensive rat (SHR), a putative animal model of Attention-Deficit/Hyperactivity Disorder (ADHD), have demonstrated increased sensitivity to many drugs of abuse, including psychostimulants. Therefore, it was suggested that studies in SHR may help elucidate ADHD and comorbidity with substance use disorder (SUD). However, the drug intake profile of the SHR in the most relevant animal model of drug addiction, the self-administration (SA) test, and its response on the conditioned place preference (CPP) paradigm are not yet determined. In the present study, we employed SA and CPP tests to investigate the reinforcing effects of the psychostimulant methamphetamine in an SHR substrain obtained from Charles River, Japan (SHR/NCrlCrlj). Concurrent tests were also performed in Wistar rats, the strain representing "normal" heterogeneous population. To address if the presence of ADHD behaviors further increases sensitivity to the rewarding effect of methamphetamine during adolescence, a critical period for the onset of drug abuse, CPP tests were especially conducted in adolescent Wistar and SHR/NCrlCrlj. We found that the SHR/NCrlCrlj also acquired methamphetamine SA and CPP, indicating reinforcing effects of methamphetamine in this ADHD animal model. However, we did not observe increased responsiveness of the SHR/NCrlCrlj to methamphetamine in both SA and CPP assays. This indicates that the reinforcing effects of methamphetamine may be similar in strains and that the SHR/NCrlCrlj may not adequately model ADHD and increased sensitivity to methamphetamine

SUCCESSFUL FACTORS OF 540° DWIHURYEOCHAGI IN TAEKWONDO

The purpose of our study was to provide fundamental information about success factors of 540° Dwihuryeochagi in Taekwondo. Twenty Taekwondo athletes who participated in the 2012 Taekwondo Kyukpa Wang (breaking king) championship: ten successful athletes (S, age: 23.1±1.6 yrs, height: 171.0±3.5 cm, body mass: 66.4±7.1 kg) and ten failed athletes (F, age: 22.3±1.8 yrs, height: 172.1±5.4 cm, body mass: 64.4±4.2 kg) were selected. Three-dimensional motion analysis using a system of 3 video cameras with a sampling of 60 fields/s was performed during the competition of 540 ° Dwihuryeochagi. Based on the findings, it is concluded that success factors of 540° Dwihuryeochagi were horizontal velocity of COM during P1, vertical velocity of COM during P2, and the time, kick distance, velocity and angle of lower extremities of P3-P4

Geochemical and Microbial Signatures of Siboglinid Tubeworm Habitats at an Active Mud Volcano in the Canadian Beaufort Sea

During the ARA08C expedition in 2017, sediment push cores were collected at an active mud volcano (420 m water depth) in the Canadian Beaufort Sea from two visually discriminative siboglinid tubeworm (ST) habitats that were colonized densely and less densely (ST1 and ST2, respectively). In this study, we investigated the biogeochemical and microbial community characteristics at ST1 by analyzing the geochemical properties, microbial lipids, and nucleic acid signatures, and comparing them with the data previously reported from ST2. The two ST sites showed distinct differences in vertical geochemical gradients [methane, sulfate, dissolved inorganic carbon (DIC), total organic carbon, and total sulfur], with a higher methane flux recorded at ST1 (0.05 mmol cm–2 y–1) than at ST2 (0.01 mmol cm–2 y–1). Notably, the δ13C values of DIC were more depleted at ST1 than at ST2, resulting in a higher proportion of DIC derived from the anaerobic oxidation of methane (AOM) at ST1 than at ST2. Moreover, both the ST1 and ST2 sites revealed the dominance of AOM-related lipid biomarkers (especially sn-2-hydroxyarchaeol), showing highly 13C-depleted values. The 16S rRNA analyses showed the presence of AOM-related archaea, predominantly anaerobic methanotrophic archaea (ANME)-3 at ST1 and ST2. Our results suggest that AOM-related byproducts (sulfide and DIC) potentially derived from ANME-3 were more abundant at ST1 than at ST2. This variation was attributed to the intensity and persistence of ascending methane. Therefore, our study suggests that AOM-derived byproducts are possibly an essential energy source for tubeworms during chemosynthetic metabolism, shaping different colony types on the seafloor

Lithium Isotope Geochemistry in the Barton Peninsula, King George Island, Antarctica

Lithium (Li) has two stable isotopes, 6Li and 7Li, whose large relative mass difference is responsible for significant isotopic fractionation during physico-chemical processes, allowing Li isotopes to be a good tracer of continental chemical weathering. Although physical erosion is dominant in the Polar regions due to glaciers, increasing global surface temperature may enhance chemical weathering, with possible consequences on carbon biogeochemical cycle and nutriment flux to the ocean. Here, we examined elemental and Li isotope geochemistry of meltwaters, suspended sediments, soils, and bedrocks in the Barton Peninsula, King George Island, Antarctica. Li concentrations range from 8.7 nM to 23.3 μM in waters, from 0.01 to 1.43 ppm in suspended sediments, from 9.56 to 36.9 ppm in soils, and from 0.42 to 28.3 ppm in bedrocks. δ7Li values are also variable, ranging from +16.4 to +41.1‰ in waters, from −0.4 to +13.4‰ in suspended sediments, from −2.5 to +6.9‰ in soils, and from −1.8 to +11.7‰ in bedrocks. Elemental and Li isotope geochemistry reveals that secondary phase formation during chemical weathering mainly control dissolved δ7Li values, rather than a mixing with sea salt inputs from atmosphere or ice melting. Likewise, δ7Li values of suspended sediments and soils lower than those of bedrocks indicate modern chemical weathering with mineral neoformation. This study suggests that increasing global surface temperature enhances modern chemical weathering in Antarctica, continuing to lower δ7Li values in meltwater with intense water-rock interactions

Reduction of Functionally Graded Material Layers for Si 3 N 4 -Al 2 O 3 System Using Three-Dimensional Finite Element Modeling

Numerical analysis method was used to reduce the number of functionally graded material (FGM) layers for joining Si 3 N 4 -Al 2 O 3 using polytypoid interlayer by estimating the position of crack. In the past, hot press sintering of multi-layered FGMs with 20 layers of thickness 500 mm each have been fabricated successfully. In this paper, thermal residual stresses were calculated using finite element method (FEM) to find the optimized number of layers and its thicknesses of FGM joint. The number of layers for FGM was reduced to 15 layers from 20 layers. Thicknesses were varied to minimize residual stresses within the layers while reducing the number of FGM layers. The damage caused by thermal residual stress was estimated using maximum principal stress theory and maximum tensile stress theory. The calculated maximum stress was found to be axial stress of 430 MPa around 90% 12H/10% Al 2 O 3 area. For each case, calculated strength of each FGM layer by linear rule of mixture was compared with computed thermal residual stresses. Thermal analysis results correctly predicted the position of crack, and this position agreed well with fabricated joints. Therefore, this numerical analysis method can be applied to reduced FGM layers of crack free joint. Finally, new composition profile of crack free joint was proposed using FGM method

Physicochemical factors that affect electroporation of lung cancer and normal cell lines

Electroporation is used for cancer therapy to efficiently destroy cancer tissues by transferring anticancer drugs into cancer cells or by irreversible tumor ablation without resealing pores. There is growing interest in the electroporation method for the treatment of lung cancer, which has the highest mortality rate among cancers. Improving the cancer cell selectivity has the potential to expand its use. However, the factors that influence the cell selectivity of electroporation are debatable. We aimed to identify the important factors that influence the efficiency of electroporation in lung cells. The electropermeabilization of lung cancer cells (H460, A549, and HCC1588) and normal lung cells (MRCS, WI26 and L132) was evaluated by the transfer of fluorescence dyes. We found that membrane permeabilization increased as cell size, membrane stiffness, resting transmembrane potential, and lipid cholesterol ratio increased. Among them, lipid composition was found to be the most relevant factor in the electroporation of lung cells. Our results provide insight into the differences between lung cancer cells and normal lung cells and provide a basis for enhancing the sensitivity of lung cancers cells to electroporation. (C) 2019 Elsevier Inc. All rights reserved.N

Exploring the pore fluid origin and methane-derived authigenic carbonate properties in response to changes in the methane flux at the southern Ulleung Basin, South Korea

We investigated the geochemistry of gas, pore fluid, and methane-derived authigenic carbonate (MDAC) from four sites in the southern Ulleung Basin, South Korea. In contrast to Sites 16GH-P1 and 16GH-P5, Sites 16GH-P3, and 16GH-P4 are characterized by acoustic chimney structures associated with gas flux. The composition of gas and isotopic signatures of methane (CH4) (C1/C2+ > 300, δ13CCH4 < -60‰, δDCH4 ≤ -190‰) indicate microbial source CH4 at all sites. The upward migration of CH4 can affect the chemical and isotopic properties of pore fluid and gas-related byproducts (e.g., gas hydrate (GH) and MDAC) within the shallow sediments including the current sulfate-methane transition (SMT) (< 5 meters below seafloor). Although no GH was found, elevated Cl- concentrations (maximum = 609 mM) with low δD and δ18O values in Site 16GH-P4 pore fluids delineate the influence of massive GH formation in deeper sediment. In contrast, relatively constant Cl-, δD, and δ18O values in fluids from Sites 16GH-P1, 16GH-P3, and 16GH-P5 indicate a predominant origin from seawater. Pore fluids also exhibit higher concentrations of H4SiO4, B, Mg2+, and K+, along with increasing alkalinity compared to seawater. These observations suggest that marine silicate weathering alters fluid chemistry within the sediment, affecting element and carbon cycles. High alkalinity (up to 60 mM) and Mg2+/Ca2+ ratios (> 6) alongside decreasing Ca2+ and Sr2+ concentrations imply carbonate precipitation. MDACs with diverse morphologies, mainly composed of aragonite and magnesian calcite, and characterized by low carbon isotopic values (δ13CMDAC < -31.3‰), were found at Sites 16GH-P3 and 16GH-P4. Interestingly, δ13CMDAC values at Site 16GH-P3 are clearly differentiated above and below the current SMT. High δ13CMDAC values above the SMT (> -34.3‰) suggest the combined influence of seawater and CH4 migrating upward on MDAC precipitation, whereas low δ13CMDAC values below it (< -41.6‰) indicate a predominant impact of CH4 on MDAC formation. Additionally, the vertical variation of δ18OMDAC values at Site 16GH-P4, compared to the theoretical values, reflects an association with GH dissociation and formation. Our findings improve the understanding of fluid, gas, and MDAC geochemistry in continental margin cold seeps, providing insights into global carbon and element cycles

The Protective Effects of Green Tea Extract against L-arginine Toxicity to Cultured Human Mesangial Cells

The aim of this study was to investigate whether green tea extract (GTE) has the protective effects on excess L-arginine induced toxicity in human mesangial cell. Human mesangial cells treated with L-arginine were cultured on Dulbecco's modified eagle medium in the presence and absence of inducible nitric oxide synthase (iNOS) inhibitor and GTE. The cell proliferation was determined by 3 (4,5-dimethylthiazol-2-yl)-2, 5-diphengltetrqzolium bromide, a tetrazole assay. The iNOS mRNA and its protein expression were detected by reverse transcription polymerase chain reaction and Western blot, respectively. The concentration of nitric oxide (NO) was measured by NO enzyme-linced immuno sorbent assay kit. L-arginine significantly inhibited the proliferation of human mesangial cells, and induced the secretion of NO to the media. NO production by L-arginine was significantly suppressed by GTE and iNOS inhibitor (p<0.01). The expression level of iNOS mRNA and its protein that was significantly increased by L-arginine was decreased by iNOS inhibitor but not by GTE. GTE protected the mesangial cells from the NO-mediated cytotoxicity by scavenging the NO rather than by iNOS gene expression. Therefore, we conclude that GTE has some protective effect for renal cells against oxidative injury possibly by polyphenols contained in GTE