CD44 signaling through focal adhesion kinase and its anti-apoptotic effect

Adhesion molecules can initiate intracellular signaling. Engagement of CD44 either by its natural ligand hyaluronan or a specific antibody on a cell line induced tyrosine phosphorylation and activation of focal adhesion kinase (FAK), which then associated with phosphatidylinositol 3-kinase (PI3K) and activated mitogen-activated protein kinase at its downstream. However, the introduction of dominant negative Rho into the cells inhibited the CD44-stimulated FAK phosphorylation. Cells expressing CD44 were significantly resistant to etoposide-induced apoptosis. This anti-apoptotic effect was cancelled by the inhibition of either Rho, FAK or PI3K. These results may indicate a signaling pathway from CD44 to mediate the resistance against drug-induced apoptosis in cancer cells.     

Integrin-Associated Protein Promotes Neuronal Differentiation of Neural Stem/Progenitor Cells

Neural stem/progenitor cells (NSPCs) proliferate and differentiate depending on their intrinsic properties and local environment. During the development of the mammalian nervous system, NSPCs generate neurons and glia sequentially. However, little is known about the mechanism that determines the timing of switch from neurogenesis to gliogenesis. In this study, we established a culture system in which the neurogenic potential of NSPCs is decreased in a time-dependent manner, so that short-term-cultured NSPCs differentiate into more neurons compared with long-term-cultured NSPCs. We found that short-term-cultured NSPCs express high levels of integrin-associated protein form 2 (IAP2; so-called CD47) mRNA using differential display analysis. Moreover, IAP2 overexpression in NSPCs induced neuronal differentiation of NSPCs. These findings reveal a novel mechanism by which IAP2 induces neuronal differentiation of NSPCs.     

Isoflurane anesthesia inhibits clozapine- and risperidone-induced dopamine release and anesthesia-induced changes in dopamine metabolism was modified by fluoxetine in the rat striatum: an in vivo microdialysis study

Previously, we have reported that halothane anesthesia increases the extracellular concentrations of dopamine (DA) metabolites in the rat striatum using in vivo microdialysis techniques, and we have suggested that volatile anesthetics affect DA release and metabolism in various ways. The present investigation assesses the effect of isoflurane, widely used in clinical anesthesia, on DA release and metabolism. A microdialysis probe was implanted in the striatum of male Sprague-Dawley rats (n=5-7 per group). After recovery, the probe was perfused with modified Ringer's solution and 40 microl of dialysate were injected into a high performance liquid chromatograph every 20 min. The rats were given saline or the same volume of 10 mg kg(-1) clozapine, risperidone, fluoxetine or citalopram. After the pharmacological treatment, the rats were anesthetized with 1.0% or 2.5% isoflurane for 1h. The data were analyzed using two-way analysis of variance (ANOVA). For each drug with significant (p<0.05) drug-time interactions, the statistical analysis included one-way ANOVA and Newman-Keuls post hoc comparisons. A high concentration of isoflurane (2.5%) anesthesia increased the extracellular concentration of DA metabolites during emergence from anesthesia. The levels of DA metabolites increased in an isoflurane concentration-dependent manner. Isoflurane attenuated DA release induced by clozapine and risperidone. Fluoxetine, but not citalopram, antagonized the isoflurane-induced increase in metabolites. The results of current investigation suggest that isoflurane enhances presynaptic DA metabolism, and that the oxidation of DA might be partially modulated by the activities of the dopaminergic-serotonergic pathway at a presynaptic site in the rat striatum.     

Identification of dicarboxylate carrier Slc25a10 as malate transporter in de novo fatty acid synthesis

Mitochondrial solute carrier family 25 member 10 (Slc25a10) transports dicarboxylates such as malate or succinate across the mitochondrial inner membrane. Although fatty acid synthesis in adipose tissue or the liver is initiated by citrate transport in exchange for malate across the mitochondrial membrane, the transporter responsible for supplying malate during citrate transport has not been identified. In the present study, we clarified the role of Slc25a10 in supplying malate for citrate transport and examined the effect of Slc25a10 suppression on the lipogenic pathway and lipid accumulation. We have reported an Slc25a10 increase in white adipose tissue in obese mouse models and a decrease in a fasted mouse model using expression profiles. Next, we examined the effect of Slc25a10 suppression by small interfering RNA on citrate transport in the lipogenic cell lines HepG2 and 3T3-L1. We observed that inhibition of malate transport by Slc25a10 suppression significantly reduced the citrate transport from the mitochondria to the cytosol. We also found that suppression of Slc25a10 down-regulated the lipogenic pathway, indicated by decreases in ACC1 expression and malonyl-CoA level. Furthermore, suppression of Slc25a10 decreased triglyceride lipid accumulation in adipose-differentiated 3T3-L1 cells. These results suggested that Slc25a10 plays an important role in supplying malate for citrate transport required for fatty acid synthesis and indicated that inhibition of Slc25a10 might effectively reduce lipid accumulation in adipose tissues.     

The amino acid sequence of the calmodulin obtained from sea anemone (Metridium senile) muscle

The amino acid sequence of the calmodulin obtained from sea anemone muscle was determined. The calmodulin was composed of 148 amino acid residues and its amino terminal was blocked. When compared with bovine brain calmodulin, the number of amino acid residues per molecule was the same and there were 3 replacements at residues 99 (Tyr → Phe), 143 (Gln → Lys) and 147 (Ala → Ser).     

Growth form-dependent response to physical disturbance and thermal stress in Acropora corals

To predict the community structure in response to changing environmental conditions, it is necessary to know the species-specific reaction and relative impact strength of each disturbance. We investigated the coral communities in two sites, an exposed and a protected site, at Iriomote Island, Japan, from 2005 to 2008. During the study period, a cyclone and thermal stress were observed. All Acropora colonies, classified into four morphologies (arborescent, tabular, corymbose, and digitate), were identified and tracked through time to calculate the annual mortality and growth rate. The mortality of all Acropora colonies in the protected site was lower than that in the exposed site during the period without disturbances. Extremely higher mortality due to bleaching was observed in tabular and corymbose Acropora, compared to other growth forms, at the protected sites after thermal stress. In contrast, physical disturbance by a tropical cyclone induced the highest mortality in arborescent and digitate corals at the exposed site. Moreover, arborescent corals exhibited a remarkable decline 1 year after the tropical cyclone at the exposed site. The growth of colonies that survived coral bleaching did not decrease in the following year compared to previous year for all growth forms, but the growth of arborescent and tabular remnant corals at the exposed site declined severely after the tropical cyclone compared to previous year. The delayed mortality and lowered growth rate after the tropical cyclone were probably due to the damage caused by the tropical cyclone. These results indicate that the cyclone had a greater impact on fragile corals than expected. This study provides useful information for the evaluation of Acropora coral response to progressing global warming conditions, which are predicted to increase in frequency and intensity in the near future.     

Optically active components and light attenuation in an offshore station of Harima Sound, eastern Seto Inland Sea, Japan

In the eastern Seto Inland Sea, Japan, phytoplankton abundance in the surface water has gradually declined, whereas Secchi depth has risen in recent years, particularly in offshore areas. Therefore, it may be hypothesized that phytoplankton dominate light attenuation in the offshore area, and that other constituents are less important. To test this hypothesis, we examined the roles of seawater, colored dissolved organic matter (CDOM), non-algal particles (tripton), and phytoplankton in the light attenuation at an offshore station of Harima Sound in the eastern Sea. The magnitude of light attenuation was then determined from the attenuation coefficient of photosynthetically available radiation (PAR) through the water column (K _d). During a 13-month period, K _d ranged from 0.179 to 0.507 m^?1, with a mean of 0.262 m^?1. The mean relative contributions of seawater (15%) and CDOM (13%) to K _d were small, while the most dominant K _d constituent was tripton (45%). The mean contribution of phytoplankton to K _d (27%) was consequently less than that of tripton. However, 75% of the temporal variability in K _d was attributed to phytoplankton, measured as chlorophyll a. Our results emphasize that the main component of light attenuation does not always govern the temporal variation of light attenuation in coastal regions.     

Population dynamics of Marginopora kudakajimensis Gudmundsson (Foraminifera: Soritidae) in the Ryukyu Islands, the subtropical northwest Pacific

The population dynamics of Marginopora kudakajimensis Gudmundsson, a dinoflagellate endosymbiont-bearing soritid foraminifer, was studied in the Ryukyu Islands, the subtropical northwest Pacific. Macroalgal samples were collected monthly between November 1995 and November 1996 at a 1-m-deep lagoonal site colonized by this species. Monthly variations in the size–frequency distributions and population density indicate that this foraminiferal population replaces itself in one year. Asexual reproduction occurs twice a year, in late spring and winter; in late spring, some of the adult individuals reproduce by multiple fission simultaneously. As a result, two cohorts (a late spring and a winter cohort) are found in the population during a year. Life span of the former cohort is up to one year, while that of the latter cohort is up to six months. Megalospheric specimens comprise up to 99% of the population with a few microspheric individuals throughout the year. The life tables and survivorship curves revealed that size-specific mortality rates were very low during the first several size classes and increased thereafter, indicating low juvenile mortality with high mortality later in life. The carbonate production rate by this Marginopora population is approximately 5 kg CaCO₃ m⁻² yr⁻¹, which is extremely higher than those reported for other larger foraminiferal species.     

A Drosophila dopamine transporter mutant,fumin (fmn), is defective in arousal regulation

Sleep and Biological Rhythms - Physiologically, sleep is defined by electroencephalography, and typical REM and NREM sleep occur only in mammalian and avian species. But sleep-like inactive states...