Systemic L-Kynurenine sulfate administration disrupts object recognition memory, alters open field behavior and decreases c-Fos immunopositivity in C57Bl/6 mice

L-Kynurenine (L-KYN) is a central metabolite of tryptophan degradation through the kynurenine pathway (KP). The systemic administration of L-KYN sulfate (L-KYNs) leads to a rapid elevation of the neuroactive KP metabolite kynurenic acid (KYNA). An elevated level of KYNA may have multiple effects on the synaptic transmission, resulting in complex behavioral changes, such as hypoactivity or spatial working memory deficits. These results emerged from studies that focused on rats, after low-dose L-KYNs treatment. However, in several studies neuroprotection was achieved through the administration of high-dose L-KYNs. In the present study, our aim was to investigate whether the systemic administration of a high dose of L-KYNs (300 mg/bwkg; i.p.) would produce alterations in behavioral tasks (open field or object recognition) in C57BI/6j mice. To evaluate the changes in neuronal activity after L-KYNs treatment, in a separate group of animals we estimated c-Fos expression levels in the corresponding subcortical brain areas. The L-KYNs treatment did not affect the general ambulatory activity of C57BI/6j mice, whereas it altered their moving patterns, elevating the movement velocity and resting time. Additionally, it seemed to increase anxiety-like behavior, as peripheral zone preference of the open field arena emerged and the rearing activity was attenuated. The treatment also completely abolished the formation of object recognition memory and resulted in decreases in the number of c-Fos-immunopositive-cells in the dorsal part of the striatum and in the CA1 pyramidal cell layer of the hippocampus. We conclude that a single exposure to L-KYNs leads to behavioral disturbances, which might be related to the altered basal c-Fos protein expression in C57BI/6j mice

Increase in Docetaxel-Resistance of Ovarian Carcinoma-Derived RMG-1 Cells with Enhanced Expression of Lewis Y Antigen

Epithelial carcinomas of the ovary exhibit the highest mortality rate among gynecologic malignancies. Studies found that the metabolism of glycolipids or carbohydrates is associated with acquirement of anticancer drug-resistance by cancer cells. This study was to characterize possible involvement of Lewis Y (LeY) antigen in the drug-resistance of cancer cells. We transfected the α1,2-fucosyltransferase gene into human ovarian carcinoma-derived RMG-1 cells and established RMG-1-hFUT cells with enhanced expression of LeY. We determined the effects of docetaxel on the survival of cells by MTT assaying and observed the apoptosis of cells in the presence of docetaxel by flow cytometric analysis and by transmission electron microscopy. Plasma membranes and intracellular granules in RMG-1-hFUT cells were stained with anti-LeY antibody, the intensity of the staining was higher than that in control cells. The RMG-1-hFUT cells exhibited higher resistance to docetaxel than the control cells with regard to the docetaxel concentration and time course. After treatment with 10 μg/mL docetaxel for 72 h, the control cells, but not RMG-1-hFUT, contained abundant positively stained cell debris due to disintegration of the cytoskeleton. On transmission electron microscopy, although the control cells treated with docetaxel as above showed the following morphology, i.e., absence of villi, cells shrunken in size, pyknosis, agglutinated chromatin and cell buds containing nuclei in the process of apoptosis, the RMG-1-hFUT cells showed only agglutinated chromatin and vacuoles in the cytoplasm. In summary, cells with enhanced expression of LeY were shown to acquire docetaxel-resistance, indicating the possible involvement of glycoconjugates in the drug-resistance

Сучасні стратегії розвитку науки

Робоча програма з дисципліни «Стратегії розвитку науки» за спеціальністю 6.030302 «Реклама та зв’язки з громадськістю» галузі знань 0303 «Журналістика та інформація», освітньо-кваліфікаційного рівня «бакалавр». – 2016. – 48 с

Large-scale structures in the Earth’s interior: Top-down hemispherical dynamics constrained by geochemical and geophysical approaches

Geochemical and geophysical observations for large-scale structures in the Earth’s interior, particularly horizontal variations of long wavelengths such as degree-1 and degree-2 structures, are reviewed with special attention to the cause of hemispherical mantle structure. Seismic velocity, electrical conductivity, and basalt geochemistry are used for mapping the large-scale structures to discuss thermal and compositional heterogeneities and their relations to dynamics of the Earth’s interior. Seismic velocity structure is the major source of information on the Earth’s interior and provides the best spatial resolution, while electrical conductivity is sensitive to water/hydrogen contents. The composition of young basalts reflects the mantle composition, and the formation age of large-scale structures can be inferred based on the radiogenic isotopes. Thus, these different research disciplines and methods complement each other and can be combined to more concretely constrain the structures and their origins. This paper aims to integrate observations from these different approaches to obtain a better understanding of geodynamics. Together with numerical modeling results of convection in the mantle and the core, “top-down hemispherical dynamics” model of the crust-mantle-core system is examined. The results suggest that a top-down link between the supercontinents, mantle geochemical hemisphere, and inner core seismic velocity hemisphere played an essential role in formation of the large-scale structures and dynamics of the Earth’s interior

Monoclonal antibody to galactosylceramide: discrimination of structural difference in the ceramide moiety

AbstractA mouse monoclonal antibody (mAb) was developed against monohexaosylceramide. This mAb differentially reacted on thin-layer chromatograms with 3 types of galactosylceramide (GalCer) obtained from bovine brain. Structural analysis of the 3 glycolipids revealed that they consisted of the same galactose and sphingosine but of apparently different fatty acids. Among the 3 GalCers, the mAb reacted with two GalCers which contained α-hydroxy fatty acids, but not with GalCer composed of nonhydroxy fatty acids. These findings suggest not only that the mAb discriminated the fatty acid composition in the ceramide moiety of GalCer, but also that the ceramide structure defines the immunological epitope as it is known to do for the carbohydrate moiety of glycosphingolipid

Enhancive effects of Lewis y antigen on CD44-mediated adhesion and spreading of human ovarian cancer cell line RMG-I

<p>Abstract</p> <p>Background</p> <p>This study aimed to investigate the molecular structural relationship between cell adhesive molecule CD44 and Lewis y antigen, and determine the effects of Lewis y antigen on CD44-mediated adhesion and spreading of ovarian cancer cell line RMG-I and the Lewis y antigen-overexpressed cell line RMG-I-H.</p> <p>Methods</p> <p>The expression of CD44 in RMG-I and RMG-I-H cells before and after treatment of Lewis y monoclonal antibody was detected by immunocytochemistry; the expression of Lewis y antigen and CD44 was detected by Western Blot. The structural relationship between Lewis y antigen and CD44 was determined by immunoprecipitation and confocal laser scanning microscopy. The adhesion and spreading of RMG-I and RMG-I-H cells on hyaluronic acid (HA) were observed. The expression of CD44 mRNA in RMG-I and RMG-I-H cells was detected by real-time RT-PCR.</p> <p>Results</p> <p>Immunocytochemistry revealed that the expression of CD44 was significantly higher in RMG-I-H cells than in RMG-I cells (<it>P </it>< 0.01), and its expression in both cell lines was significantly decreased after treatment of Lewis y monoclonal antibody (both <it>P </it>< 0.01). Western Blot confirmed that the content of CD44 in RMG-I-H cells was 1.46 times of that in RMG-I cells. The co-location of Lewis y antigen and CD44 was confirmed by co-immunoprecipitation. The co-expression of CD44 and Lewis y antigen in RMG-I-H cells was 2.24 times of that in RMG-I cells. The adhesion and spreading of RMG-I-H cells on HA were significantly enhanced as compared to those of RMG-I cells (<it>P </it>< 0.01), and this enhancement was inhibited by Lewis y monoclonal antibody (<it>P </it>< 0.01). The mRNA level of CD44 in both cell lines was similar (<it>P </it>> 0.05).</p> <p>Conclusion</p> <p>Lewis y antigen strengthens CD44-mediated adhesion and spreading of ovarian cancer cells.</p