2-Mercaptoethylamine, a competitive inhibitor of spermidine synthase in mammalian cells

AbstractSpermidine synthase from rat ventral prostate was inhibited by 2-mercaptoethylamine (MEA). Inhibition of spermidine synthase by MEA was competitive with respect to one of the substrates putrescine, but not competitive with respect to the other substrate decarboxylated S-adenosylmethionine. MEA markedly depressed spermidine and spermine contents in human erythroid leukemia K562 cells, suggesting that these changes resulted from the inhibitory effect of MEA on spermidine synthase in situ

Microscopic synchrotron X-ray analysis of mercury waste in simulated landfill experiments

Mercury enters into the environment or waste streams because it is present as an impurity in natural minerals. Mercury must be appropriately managed as an hazardous waste. In this study, a waste layer of artificial mercury sulfide mixed with incinerator ash and sewage sludge compost in a simulated landfill experiment for 5 years was analyzed using microscopic synchrotron X-ray to obtain basic knowledge of mercury behavior in a landfill. Mapping by synchrotron X-ray revealed the distribution of mercury-containing particles in the waste layer. In most cases, the movement of mercury sulfide was not considered significant even within a microscopic range; however, water flows could enhance the movement of mercury sulfide particles. When disposing of mercury sulfide, “concentrated placement” or solidification, rather than mixing with other wastes, was more effective at preventing mercury leaching in lysimeters. The chemical form of mercury sulfide in each lysimeter was confirmed by X-ray absorption fine structure (XAFS) analysis, which showed that most of the mercury was present as metacinnabar and had not undergone any changes, indicating that it was extremely stable. The microscopic synchrotron X-ray analysis proved very useful for studying the behavior of mercury waste in a simulated landfill experiment

Sequence divergence and retrotransposon insertion underlie interspecific epigenetic differences in primates

内在性レトロウイルス配列によってヒトのエピゲノムが変化してきたことを発見！ --ヒトとチンパンジーのiPS細胞の比較解析から--. 京都大学プレスリリース. 2022-10-12.Changes in the epigenome can affect the phenotype without the presence of changes in the genomic sequence. Given the high identity of the human and chimpanzee genome sequences, a substantial portion of their phenotypic divergence likely arises from epigenomic differences between the two species. In this study, the transcriptome and epigenome were determined for induced pluripotent stem cells (iPSCs) generated from human and chimpanzee individuals. The transcriptome and epigenomes for trimethylated histone H3 at lysine-4 (H3K4me3) and lysine-27 (H3K27me3) showed high levels of similarity between the two species. However, there were some differences in histone modifications. Although such regions, in general, did not show significant enrichment of interspecies nucleotide variations, gains in binding motifs for pluripotency-related transcription factors, especially POU5F1 and SOX2, were frequently found in species-specific H3K4me3 regions. We also revealed that species-specific insertions of retrotransposons, including the LTR5_Hs subfamily in human and a newly identified LTR5_Pt subfamily in chimpanzee, created species-specific H3K4me3 regions associated with increased expression of nearby genes. Human iPSCs have more species-specific H3K27me3 regions, resulting in more abundant bivalent domains. Only a limited number of these species-specific H3K4me3 and H3K27me3 regions overlap with species-biased enhancers in cranial neural crest cells, suggesting that differences in the epigenetic state of developmental enhancers appear late in development. Therefore, iPSCs serve as a suitable starting material for studying evolutionary changes in epigenome dynamics during development

Spatially Resolved Spectral Imaging by A THz-FEL

Using the unique characteristics of the free-electron-laser (FEL), we successfully performed high-sensitivity spectral imaging of different materials in the terahertz (THz) and far-infrared (FIR) domain. THz imaging at various wavelengths was achieved using in situ spectroscopy by means of this wavelength tunable and monochromatic source. In particular, owing to its large intensity and directionality, we could collect high-sensitivity transmission imaging of extremely low-transparency materials and three-dimensional objects in the 3–6 THz range. By accurately identifying the intrinsic absorption wavelength of organic and inorganic materials, we succeeded in the mapping of spatial distribution of individual components. This simple imaging technique using a focusing optics and a raster scan modality has made it possible to set up and carry out fast spectral imaging experiments on different materials in this radiation facility

Observation of Enhanced Radial Transport of Energetic Ion due to Energetic Particle Mode Destabilized by Helically-trapped Energetic Ion in the Large Helical Device

A deuterium experiment was initiated to achieve higher-temperature and higher-density plasmas in March 2017 in the Large Helical Device (LHD). The central ion temperature notably increases compared with that in hydrogen experiments. However, an energetic particle mode called the helically-trapped energetic-ion-driven resistive interchange (EIC) mode is often excited by intensive perpendicular neutral beam injections on high ion-temperature discharges. The mode leads to significant decrease of the ion temperature or to limiting the sustainment of the high ion-temperature state. To understand the effect of EIC on the energetic ion confinement, the radial transport of energetic ions is studied by means of the neutron flux monitor and vertical neutron camera newly installed on the LHD. Decreases of the line-integrated neutron profile in core channels show that helically-trapped energetic ions are lost from the plasma

Effect of the helically-trapped energetic-ion-driven resistive interchange modes on energetic ion confinement in the Large Helical Device

The effect of the helically-trapped energetic-ion-driven resistive interchange modes (EICs) on energetic ion confinement is studied in the Large Helical Device deuterium plasmas. Neutron diagnostics such as the neutron flux monitor and the vertical neutron camera (VNC) are used in order to measure neutrons mainly created by beam-plasma reactions. The line-integrated neutron profiles are obtained by VNC in magnetohydrodynamic-quiet plasma with various neutral beam (NB) injection patterns. The profiles are consistent with that expected by the beam ion density calculated using orbit-following simulations. Significant decreases of the total neutron emission rate (Sn) and the neutron counting rate of the VNC (Cn) in central cords are observed to be synchronized with EIC bursts with perpendicular-NB injection. The drop rates of both Sn and Cn increase with EIC amplitude and reach around 50%. The line-integrated neutron profiles before and after EIC burst show that in the central cords, Cn decrease due to EIC burst whereas there is almost no change in the other cords. The experimental results suggests that the effect of EIC on helically-trapped beam ion is substantial, however the effect of passing beam ion is not significant

X-ray harmonic comb from relativistic electron spikes

X-ray devices are far superior to optical ones for providing nanometre spatial and attosecond temporal resolutions. Such resolution is indispensable in biology, medicine, physics, material sciences, and their applications. A bright ultrafast coherent X-ray source is highly desirable, for example, for the diffractive imaging of individual large molecules, viruses, or cells. Here we demonstrate experimentally a new compact X-ray source involving high-order harmonics produced by a relativistic-irradiance femtosecond laser in a gas target. In our first implementation using a 9 Terawatt laser, coherent soft X-rays are emitted with a comb-like spectrum reaching the 'water window' range. The generation mechanism is robust being based on phenomena inherent in relativistic laser plasmas: self-focusing, nonlinear wave generation accompanied by electron density singularities, and collective radiation by a compact electric charge. The formation of singularities (electron density spikes) is described by the elegant mathematical catastrophe theory, which explains sudden changes in various complex systems, from physics to social sciences. The new X-ray source has advantageous scalings, as the maximum harmonic order is proportional to the cube of the laser amplitude enhanced by relativistic self-focusing in plasma. This allows straightforward extension of the coherent X-ray generation to the keV and tens of keV spectral regions. The implemented X-ray source is remarkably easily accessible: the requirements for the laser can be met in a university-scale laboratory, the gas jet is a replenishable debris-free target, and the harmonics emanate directly from the gas jet without additional devices. Our results open the way to a compact coherent ultrashort brilliant X-ray source with single shot and high-repetition rate capabilities, suitable for numerous applications and diagnostics in many research fields

Overexpression of optineurin E50K disrupts Rab8 interaction and leads to a progressive retinal degeneration in mice

Glaucoma is one of the leading causes of bilateral blindness affecting nearly 8 million people worldwide. Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs) and is often associated with elevated intraocular pressure (IOP). However, patients with normal tension glaucoma (NTG), a subtype of primary open-angle glaucoma (POAG), develop the disease without IOP elevation. The molecular pathways leading to the pathology of NTG and POAG are still unclear. Here, we describe the phenotypic characteristics of transgenic mice overexpressing wild-type (Wt) or mutated optineurin (Optn). Mutations E50K, H486R and Optn with a deletion of the first (amino acids 153–174) or second (amino acids 426–461) leucine zipper were used for overexpression. After 16 months, histological abnormalities were exclusively observed in the retina of E50K mutant mice with loss of RGCs and connecting synapses in the peripheral retina leading to a thinning of the nerve fiber layer at the optic nerve head at normal IOP. E50K mice also showed massive apoptosis and degeneration of entire retina, leading to approximately a 28% reduction of the retina thickness. At the molecular level, introduction of the E50K mutation disrupts the interaction between Optn and Rab8 GTPase, a protein involved in the regulation of vesicle transport from Golgi to plasma membrane. Wt Optn and an active GTP-bound form of Rab8 complex were localized at the Golgi complex. These data suggest that alternation of the Optn sequence can initiate significant retinal degeneration in mice