Neuronal apoptosis and inflammatory responses in the central nervous system of a rabbit treated with Shiga toxin-2

<p>Abstract</p> <p>Background</p> <p>Shiga toxins (Stxs) are the major agents responsible for hemorrhagic colitis and hemolytic-uremic syndrome (HUS) during infections caused by Stx-producing <it>Escherichia coli </it>(STEC) such as serotype O157:H7. Central nervous system (CNS) involvement is an important determinant of mortality in diarrhea associated-HUS. It has been suggested that vascular endothelial injuries caused by Stxs play a crucial role in the development of the disease. The current study investigates the relationship between the cytotoxic effects of Stxs and inflammatory responses in a rabbit brain treated with Stx2.</p> <p>Methods</p> <p>In a rabbit model treated with purified Stx2 or PBS(-), we examined the expression of the Stx receptor globotriaosylceramide (Gb3)/CD77 in the CNS and microglial activation using immunohistochemistry. The relationship between inflammatory responses and neuronal cell death was analyzed by the following methods: real time quantitative reverse transcriptase (RT)-polymerase chain reaction (PCR) to determine the expression levels of pro-inflammatory cytokines, and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method to detect apoptotic changes.</p> <p>Results</p> <p>Gb3/CD77 expression was detected in endothelial cells but not in neurons or glial cells. In the spinal cord gray matter, significant levels of Gb3/CD77 expression were observed. Severe endothelial injury and microvascular thrombosis resulted in extensive necrotic infarction, which led to acute neuronal damage. Conversely, in the brain, Stx receptor expression was much lower. The observed neuropathology was less severe. However, neuronal apoptosis was observed at the onset of neurological symptoms, and the number of apoptotic cells significantly increased in the brain at a later stage, several days after onset. Microglial activation was observed, and tumor necrosis factor (TNF)-α and interleukin (IL)-1β mRNA in the CNS parenchyma was significantly up-regulated. There was significant overexpression of TNF-α transcripts in the brain.</p> <p>Conclusion</p> <p>This study indicates that Stx2 may not directly damage neural cells, but rather inflammatory responses occur in the brain parenchyma in response to primary injury by Stx2 in vascular endothelial cells expressing Gb3/CD77. These findings suggest that neuroinflammation may play a critical role in neurodegenerative processes during STEC infection and that anti-inflammatory intervention may have therapeutic potential.</p

Response time differences during hand mental rotation

This study explored gender differences in correct response rates and response times on a task involving left or right arrow selection and another involving the transformation of mental rotation of the hand. We recruited 15 healthy, right-handed men (age 24.5 ± 6.4) and 15 healthy, right-handed women (age 21.3 ± 4.9). For the tasks, we used pictures of left and right arrows and 32 hand pictures (left and right, palm and back) placed in cons (each at 45° from 0° to 315°). Hand and arrow pictures alternated and were shown at random. Participants decided as quickly as possible whether each picture was left or right. To compare the time taken for the transformation of mental rotation of the hand, we subtracted the average arrow response time from that for the left and right hand pictures for each participant. Correct response rates did not differ significantly between men and women or left and right for either arrow or hand pictures. Regardless of gender, the response time was longer for the left arrow picture than right arrow picture. The response time for the hand picture was longest for both men and women for pictures at rotation angles that were most difficult to align with participants’ hands. While there was no difference between men’s responses for left and right hand pictures, the responses of women were longer for left than right hand pictures and also than those of men. These findings suggest that both men and women mainly perform the hand mental rotation task with implicit motor imagery. On the other hand, the gender difference in performance might be explained by the difference in balance with other strategies, such as visual imagery, and by cognitive, neurophysiological, and morphological differences

Simulation of feedback instability in the coupled magnetosphere-ionosphere system

[1] Quiet auroral arcs formation has been investigated theoretically and numerically in a self-consistent dynamic way. By using a three-dimensional magneto-hydro-dynamics simulation of a dipole magnetosphere-ionosphere coupling system, it is shown that multiple longitudinally striated structures of the ionospheric plasma density and the field-aligned current are formed, resulting from nonlinear feedback instability. The areas where these structures appear are consistent with the prediction by the integrated feedback theory that includes the effects of the spatially non-uniform electric field and non-uniform plasma density. Effects of the difference of the field line lengths between the ionosphere and the magnetospheric equator over the auroral latitudes are also discussed on the feedback instability

Preparation of Cu-doped TiO2 via refluxing of alkoxide solution and its photocatalytic properties

Cu-doped TiO2 was prepared by the refluxing of a mixture of copper and titanium alkoxides. The refluxing improved the Cu2+ dispersion in the TiO2 and formed effective Ti-O-Cu bonds. The impurity states due to the highly dispersed Cu2+ were presumed to trap the electrons in the conduction band of the TiO2 and prevent charge recombination of the electrons and holes. Consequently, the prolonged charge separation duration was suggested to enhance the photocatalytic activity of the Cu-doped TiO2. This enhancement was confirmed by the hydroxyl radical generation and organic compound degradation. The Ti-O-Cu bonds and electronic interaction between Cu and Ti should effectively promote the electron trapping. The Cu-doped TiO2 exhibited a visible light-induced activity due to the transition from the TiO2 valence band to the Cu2+ impurity states.ArticleRESEARCH ON CHEMICAL INTERMEDIATES. 38(2):595-613 (2012)journal articl

Functional network of glycan-related molecules: Glyco-Net in Glycoconjugate Data Bank

<p>Abstract</p> <p>Background</p> <p>Glycans are involved in a wide range of biological process, and they play an essential role in functions such as cell differentiation, cell adhesion, pathogen-host recognition, toxin-receptor interactions, signal transduction, cancer metastasis, and immune responses. Elucidating pathways related to post-translational modifications (PTMs) such as glycosylation are of growing importance in post-genome science and technology. Graphical networks describing the relationships among glycan-related molecules, including genes, proteins, lipids and various biological events are considered extremely valuable and convenient tools for the systematic investigation of PTMs. However, there is no database which dynamically draws functional networks related to glycans.</p> <p>Description</p> <p>We have created a database called Glyco-Net <url>http://www.glycoconjugate.jp/functions/</url>, with many binary relationships among glycan-related molecules. Using search results, we can dynamically draw figures of the functional relationships among these components with nodes and arrows. A certain molecule or event corresponds to a node in the network figures, and the relationship between the molecule and the event are indicated by arrows. Since all components are treated equally, an arrow is also a node.</p> <p>Conclusions</p> <p>In this paper, we describe our new database, Glyco-Net, which is the first database to dynamically show networks of the functional profiles of glycan related molecules. The graphical networks will assist in the understanding of the role of the PTMs. In addition, since various kinds of bio-objects such as genes, proteins, and inhibitors are equally treated in Glyco-Net, we can obtain a large amount of information on the PTMs.</p

DNA Methylation Profiling of Embryonic Stem Cell Differentiation into the Three Germ Layers

Embryogenesis is tightly regulated by multiple levels of epigenetic regulation such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent developmental reprogramming occurs by de novo methylation and demethylation. Variance in DNA methylation patterns between different cell types is not well understood. Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analyzed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm). Most of the methylated regions are methylated across all three germ layers and in the three adult somatic tissues. This commonly methylated gene set is enriched in germ cell-associated genes that are generally transcriptionally inactive in somatic cells. We also compared DNA methylation patterns by global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation. Our combined findings indicate that differentiation of ES cells into the three germ layers is accompanied by an increased number of commonly methylated DNA regions and that these tissue-specific alterations in methylation occur for only a small number of genes. DNA methylation at the proximal promoter regions of commonly methylated genes thus appears to be an irreversible mark which functions to fix somatic lineage by repressing the transcription of germ cell-specific genes

Measurement of the mechanical loss of a cooled reflective coating for gravitational wave detection

We have measured the mechanical loss of a dielectric multilayer reflective coating (ion-beam sputtered SiO$_2$ and Ta$_2$O$_5$) in cooled mirrors. The loss was nearly independent of the temperature (4 K $\sim$ 300 K), frequency, optical loss, and stress caused by the coating, and the details of the manufacturing processes. The loss angle was $(4 \sim 6) \times 10^{-4}$. The temperature independence of this loss implies that the amplitude of the coating thermal noise, which is a severe limit in any precise measurement, is proportional to the square root of the temperature. Sapphire mirrors at 20 K satisfy the requirement concerning the thermal noise of even future interferometric gravitational wave detector projects on the ground, for example, LCGT.Comment: 8 pages, 6 figures, 3 tables : accepted version (by Physical Review D