Activation of channel activity of the NMDA receptor-PSD-95 complex by guanylate kinase-associated protein (GKAP)

AbstractThe channel-associated protein PSD-95 functionally modulates NMDA receptor channels, interacting with the channels via PDZ domain of PSD-95. PSD-95 also interacts with guanylate kinase-associated protein (GKAP) through the guanylate kinase-like domain of PSD-95. Here we report that GKAP markedly potentiates the channel activity of the receptor-PSD-95 complex. However, GKAP had no effect on basic properties of the channels nor on PSD-95-induced changes in channel properties. Thus, GKAP affects the channel activity of the NMDA receptor via PSD-95 quantitatively, which may make signal transmission more efficient at postsynaptic sites

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The shielding ability of the ultraviolet rays (UV-ray) through fabrics were inves tigated by the measurement of the transmittance of the UV-ray (the sun\u27 rays) through the fabrics. UV-ray shielding efficiency of fabrics are influenced by fabric construction, thick ness, color and fluorescent whitening agent. UV-ray shielding efficiency of "UV-cut fabrics" does not change very much as compared with general fabrics

Breast cancer cell lines carry cell line-specific genomic alterations that are distinct from aberrations in breast cancer tissues: Comparison of the CGH profiles between cancer cell lines and primary cancer tissues

<p>Abstract</p> <p>Background</p> <p>Cell lines are commonly used in various kinds of biomedical research in the world. However, it remains uncertain whether genomic alterations existing in primary tumor tissues are represented in cell lines and whether cell lines carry cell line-specific genomic alterations. This study was performed to answer these questions.</p> <p>Methods</p> <p>Array-based comparative genomic hybridization (CGH) was employed with 4030 bacterial artificial chromosomes (BACs) that cover the genome at 1.0 megabase resolution to analyze DNA copy number aberrations (DCNAs) in 35 primary breast tumors and 24 breast cancer cell lines. DCNAs were compared between these two groups. A tissue microdissection technique was applied to primary tumor tissues to reduce the contamination of samples by normal tissue components.</p> <p>Results</p> <p>The average number of BAC clones with DCNAs was 1832 (45.3% of spotted clones) and 971 (24.9%) for cell lines and primary tumor tissues, respectively. Gains of 1q and 8q and losses of 8p, 11q, 16q and 17p were detected in >50% of primary cancer tissues. These aberrations were also frequently detected in cell lines. In addition to these alterations, the cell lines showed recurrent genomic alterations including gains of 5p14-15, 20q11 and 20q13 and losses of 4p13-p16, 18q12, 18q21, Xq21.1 and Xq26-q28 that were barely detected in tumor tissue specimens. These are considered to be cell line-specific DCNAs. The frequency of the HER2 amplification was high in both cell lines and tumor tissues, but it was statistically different between cell lines and primary tumors (P = 0.012); 41.3 ± 29.9% for the cell lines and 15.9 ± 18.6% for the tissue specimens.</p> <p>Conclusions</p> <p>Established cell lines carry cell lines-specific DCNAs together with recurrent aberrations detected in primary tumor tissues. It must therefore be emphasized that cell lines do not always represent the genotypes of parental tumor tissues.</p

A Meta-Analysis of Array-CGH Studies Implicates Antiviral Immunity Pathways in the Development of Hepatocellular Carcinoma

BACKGROUND: The development and progression of hepatocellular carcinoma (HCC) is significantly correlated to the accumulation of genomic alterations. Array-based comparative genomic hybridization (array CGH) has been applied to a wide range of tumors including HCCs for the genome-wide high resolution screening of DNA copy number changes. However, the relevant chromosomal variations that play a central role in the development of HCC still are not fully elucidated. METHODS: In present study, in order to further characterize the copy number alterations (CNAs) important to HCC development, we conducted a meta-analysis of four published independent array-CGH datasets including total 159 samples. RESULTS: Eighty five significant gains (frequency ≥ 25%) were mostly mapped to five broad chromosomal regions including 1q, 6p, 8q, 17q and 20p, as well as two narrow regions 5p15.33 and 9q34.2-34.3. Eighty eight significant losses (frequency ≥ 25%) were most frequently present in 4q, 6q, 8p, 9p, 13q, 14q, 16q, and 17p. Significant correlations existed between chromosomal aberrations either located on the same chromosome or the different chromosomes. HCCs with different etiologies largely exhibited surprisingly similar profiles of chromosomal aberrations with only a few exceptions. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the genes affected by these chromosomal aberrations were significantly enriched in 31 canonical pathways with the highest enrichment observed for antiviral immunity pathways. CONCLUSIONS: Taken together, our findings provide novel and important clues for the implications of antiviral immunity-related gene pathways in the pathogenesis and progression of HCC

Cancer Cells Expressing Toll-like Receptors and the Tumor Microenvironment

Toll-like receptors (TLRs) play a crucial role in the innate immune response and the subsequent induction of adaptive immune responses against microbial infection or tissue injury. Recent findings show that functional TLRs are expressed not only on immune cells but also on cancer cells. TLRs play an active role in carcinogenesis and tumor progression during chronic inflammation that involves the tumor microenvironment. Damage-associated molecular patterns (DAMPs) derived from injured normal epithelial cells and necrotic cancer cells appear to be present at significant levels in the tumor microenvironment, and their stimulation of specific TLRs can foster chronic inflammation. This review discusses how carcinogenesis, cancer progression, and site-specific metastasis are related to interactions between cancer cells, immune cells, and DAMPs through TLR activation in the tumor microenvironment

Nature meets nurture: molecular genetics of gastric cancer

The immensity of genes and molecules implicated in gastric carcinogenesis is overwhelming and the relevant importance of some of these molecules is too often unclear. This review serves to bring us up-to-date with the latest findings as well as to look at the larger picture in terms of how to tackle the problem of solving this multi-piece puzzle. In this review, the environmental nurturing of intestinal cancer is discussed, beginning with epidemiology (known causative factors for inducing molecular change), an update of H. pylori research, including the role of inflammation and stem cells in premalignant lesions. The role of E-cadherin in the nature (genotype) of diffuse gastric cancer is highlighted, and finally the ever growing discipline of SNP analysis (including IL1B) is discussed

Poétique de Francis Ponge (une poétique du sujet comme altérité de l'objet)

Cette thèse se propose d étudier le fonctionnement de l œuvre du poète français Francis Ponge (1899-1988), qui, sous l aspect d une recherche de l objectivité, se révèle construire un lieu où le sujet poétique s invente comme altérité. Ce sujet qui fonde la poétique de Ponge est une altérité radicale qui engage des rapports pluriels : sujet, objet, mots, choses, mots et choses, mots ou choses, etc. sans pour autant y être réduit La description qui est en prise avec le réel ne tend pas vers une substitution de la réalité, mais pose le problème de la connaissance en tant que proble me de langage. Dans un sens opposé, l écriture allégorique cherche à déborder la condition du dire en faisant subir au langage lui-même un processus inverse de métaphorisation, qui agit comme une critique de l ontologie poétique. L étude du rythme et de la prosodie des poèmes permet d apprécier les mouvements de la parole poétique sans réduire les métaphores et les analogies au statut d objets, mais en déplaçant le point de vue extérieur de la description vers une subjectivation interne. Il s agit de rendre compte de l émergence d un sujet qui ne se reconnaît pas a priori, mais qui se présente comme quelque chose qui est toujours déjà là.This thesis examines the functioning of the works of Francis Ponge (1899-1988) which while giving the appearance of objectivity, in fact constructs a place where the poetic subject is created as an alterity. This subject which forms the basis of Ponge's poetics is a radical alterity involving several relationships: subject, object, words, things, words and things, words or things, etc. without itself being reduced. The description which conforms to the real does not attempt to substitute reality but poses the problem of knowledge as a problem of language. In an opposing sense, the allegorical text attempts to surpass the condition of creativity by submitting a reverse metaphorisation to the language itself where the metaphorisation acts as a critic of poetic ontology. The study of the rhythm and the prosody of the poems enable an appreciation of the movement of the poetic text without reducing the metaphors and the analogies to the level of objects, but by moving the point of view outside the description toward an internal subjectivation. It is a matter of understanding the emergence of the subject which is not apparent a priori but which is always there.ST DENIS-BU PARIS8 (930662101) / SudocSudocFranceF