A novel ascorbic acid-resistant nitroxide in fat emulsion is an efficient brain imaging probe for in vivo EPR imaging of mouse

The loss of paramagnetism of nitroxide radicals due to reductant reactions in biological systems, places a fundamental time constraint on their application as an imaging probe in in vivo EPR imaging studies. However, in vitro studies of the newly synthesized tetraethyl-substituted piperidine nitroxide radical demonstrated high resistivity to paramagnetic reduction when exposed to ascorbic acid, a common reduction agent in biological systems. In this work we investigated the use of these nitroxides as an imaging probe in EPR imaging of small rodents. 2,2,6,6-Tetraethyl-piperidine nitroxide (TEEPONE) is not highly soluble in aqueous media, thus a lipid-based emulsion system of lecithin was used to solubilize TEEPONE. The obtained solution was homogenous and with low viscosity, allowing smooth intravenous injection into mice tail vein. Acquired three dimensional (3D) EPR images of mouse head clearly showed TEEPONE distributed in all tissues including brain tissues, with an average measurable signal half-life of more than 80 min, thus demonstrating high resistivity to reduction due to ascorbic acid in in vivo animal studies, and the potential for use of this compound in in vivo studies of animal model systems.     

Dendrite remodeling in development and disease

One of the most important features of neuronal function is the capacity to dynamically adapt in response to changes in the environment and neuronal activity. Among cellular elements that show this kind of plasticity are dendrites, the components that receive and process neuronal inputs. Dendrite remodeling occurs during normal development of the nervous system as well as in response to injury or diseases in the adult. In either case, selective stabilization and/or elimination of dendritic branches is likely important to shape dendritic arbors. Here I review examples of the phenomena and consider potential cellular and molecular mechanisms that underlie dendrite remodeling and how they might relate in development and disease.     

Preparation and Reaction of Partially Benzylated 2-Azido-2-deoxy-l-xylopyranose

2-Azido-3,4-di-O-benzyl-2-deoxy-l-xylopyranose (XV) was prepared. Oxidation of XV with methyl sulfoxide and acetic anhydride was examined.     

Studies on the d-Xylose Series

Methyl 2-O-acetyl-3-O-methanesulfonyl-5-O-benzyl-d-xylofuranoside (X) was prepared from 1,2-O-isopropylidene-d-xylofuranose.

Solvolysis of X in methyl cellosolve in the presence of sodium acetate trihydrate gave a mixture of three pentose derivatives (xylose, arabinose and ribose). Formation of cis-2,3-diol compound (ribose) is supposed to be specific to furanose ring because solvolysis of 3-sulfonyl ester in pyranose ring, having trans-2-acetoxyl group, gave no cis-2,3-diol Compound.     

Role of interleukin-12 in determining differential kinetics of invariant natural killer T cells in response to differential burden of Listeria monocytogenes

Invariant (i) natural killer (NK) T cells are unique T lymphocytes expressing NKR-P1B/C (NK1.1), which recognize glycolipids, notably alpha-galactosylceramide (alpha-GalCer) presented by CD1d. The characteristic phenotype of these iNKT cells undergoes dramatic changes following Listeria monocytogenes infection, and interleukin (IL)-12 is involved in these alterations. Here we show that liver iNKT cells in mice are differentially influenced by the load of infection. Liver alpha-GalCer/CD1d tetramer-reactive (alpha-GalCer/CD1d(+)) T cells expressing NK1.1 became undetectable by day 2 following L. monocytogenes infection and concomitantly cells lacking NK1.1 increased regardless of the severity of infection. Whereas alpha-GalCer/CD1d(+)NK1.1(+) T cells remained virtually undetectable on day 4 following low-dose infection, considerable numbers of these cells were detected in high-dose-infected mice. Whereas numbers of IL-12 producers in the liver on day 4 post infection were comparable in low- and high-dose-infected mice without in vitro restimulation with heat-killed Listeria, those were more prominent in low-dose-infected mice than in high-dose-infected mice after restimulation despite the fact that higher numbers of macrophages and granulocytes infiltrated the liver in high-dose-infected mice than in low-dose-infected mice. Our results indicate that NK1.1 surface expression on iNKT cells is differentially modulated by the burden of infection, and suggest that a high bacterial load probably causes loss of IL-12 production.     

Chemical characterization of milk oligosaccharides of the koala (Phascolarctos cinereus)

Previous structural characterizations of marsupial milk oligosaccharides had been performed in only two macropod species, the tammar wallaby and the red kangaroo. To clarify the homology and heterogeneity of milk oligosaccharides among marsupial species, which could provide information on their evolution, the oligosaccharides of the koala milk carbohydrate fraction were characterized in this study. Neutral and acidic oligosaccharides were separated from the carbohydrate fraction of milk of the koala, a non-macropod marsupial, and characterized by ¹H-nuclear magnetic resonance spectroscopy. The structures of the neutral saccharides were found to be Gal(β1-4)Glc (lactose), Gal(β1-3)Gal(β1-4)Glc (3′-galactosyllactose), Gal(β1-3)Gal(β1-3)Gal(β1-4)Glc (3′,3″-digalactosyllactose), Gal(β1-3)[Gal(β1-4)GlcNAc(β1-6)]Gal(β1-4)Glc (lacto-N-novopentaose I) and Gal(β1-3){Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-6)}Gal(β1-4)Glc (fucosyl lacto-N-novopentaose I), while those of the acidic saccharides were Neu5Ac(α2-3)Gal(β1-4)Glc (3′-SL), Neu5Ac(α2-3)Gal(β1-3)Gal(β1-4)Gal (sialyl 3′-galactosyllactose), Neu5Ac(α2-3)Gal(β1-3)[Gal(β1-4)GlcNAc(β1-6)]Gal(β1-4)Glc (sialyl lacto-N-novopentaose a), Gal(β1-3)[Neu5Ac(α2-6)Gal(β1-4)GlcNAc(β1-6)]Gal(β1-4)Glc (sialyl lacto-N-novopentaose b), Gal(β1-3)[Neu5Ac(α2-3)Gal(β1-4)GlcNAc(β1-6)]Gal(β1-4)Glc (sialyl lacto-N-novopentaose c), and Neu5Ac(α2-3)Gal(β1-3){Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-6)}Gal(β1-4)Glc (fucosyl sialyl lacto-N-novopentaose a). The neutral oligosaccharides, other than fucosyl lacto-N-novopentaose I, a novel hexasaccharide, had been found in milk of the tammar wallaby, a macropod marsupial, while the acidic oligosaccharides, other than fucosyl sialyl lacto-N-novopentaose a had been identified in milk carbohydrate of the red kangaroo. The presence of fucosyl oligosaccharides is a significant feature of koala milk, in which it differs from milk of the tammar wallaby and the red kangaroo.     

Barriers to Cooperation Aid Ideological Rigidity and Threaten Societal Collapse

Understanding the factors that promote, disrupt, or shape the nature of cooperation is one of the main tasks of evolutionary biology. Here, we focus on attitudes and beliefs supportive of in-group favoritism and strict adherence to moral consensus, collectively known as ideological rigidity, that have been linked with both ends of the political spectrum. The presence among the political right and the left is likely to make ideological rigidity a major determinant of the political discourse with an important social function. To better understand this function, we equip the indirect reciprocity framework – widely used to explain evaluation-mediated social cooperation – with multiple stylized value systems, each corresponding to the different degree of ideological rigidity. By running game theoretical simulations, we observe the competitive evolution of these systems, map conditions that lead to more ideologically rigid societies, and identify potentially disastrous outcomes. In particular, we uncover that barriers to cooperation aid ideological rigidity. The society may even polarize to the extent where social parasites overrun the population and cause the complete collapse of the social structure. These results have implications for lawmakers globally, warning against restrictive or protectionist policies.     

α1-Antichymotrypsin inhibits chymotrypsin-induced apoptosis in rat hepatoma cells

Increased serum levels of α1-antichymotrypsin (α1ACT) are observed in some cancer patients, especially those with hepatocellular carcinoma. A possible role of α1ACT in tumour growth has been suggested, but this remains uncertain. We have demonstrated that α1ACT inhibited chymotrypsin-induced apoptosis in rat hepatoma H4 cells. Even low concentrations of chymotrypsin (but not trypsin) induce apoptosis in H4 cells with a minimum effective concentration of 2.4 × 10−2 units/ml (0.5 μg/ml), and this apoptosis was inhibited by α1ACT in a concentration-dependent manner. Furthermore, the concentrations of α1ACT required to inhibit the apoptosis were lower than normal serum levels. These results may indicate that α1ACT plays a role in the apoptosis of rat hepatoma cells. This revised version was published online in June 2006 with corrections to the Cover Date.