Aaptamine, a spongean alkaloid, activates p21 promoter in a p53-independent manner

Aaptamine, a benzonaphthyridine alkaloid was isolated from a marine sponge on the guidance of a bioassay using the transfected human osteosarcoma MG63 cells (MG63luc(+)). Aaptamine activated p21 promoter stably transfected in MG63 cells dose-dependently at the concentrations of 20-50microM. Expression of p21 and its mRNA in the wild-type MG63 cells also increased by aaptamine-treatment. Furthermore, the cell cycle of MG63 cells was arrested at the G2/M phase within 48h by the aaptamine-treatment. To analyze a responsive element of p21 promoter in the up-regulation of p21 by aaptamine, MG63 cells were transiently transfected with a series of the deleted or mutated promoter segments, and induction of luciferase with aaptamine treatment was examined by using these corresponding transfected cells. The activation of p21 promoter by aaptamine was led through acting Sp1 sites between -82 and -50bp in a p53-independent manner.     

Effects of Sex,Season and Time of Day upon Glycemic Recovery after Exercise in the Subarctic

The replenishment of blood glucose after exercise was studied in 62 healthy subjects performing a standardized exercise at 2 different times of the day in 5 different months of the year. Blood samples (fingertip) for glucose determination were drawn at the start of exercise and at 1, 5, 10 and 30 min after exercise. The total area under the glucose-time curves during the 30 min of recovery was calculated in either absolute units or as percent of the starting value. ANOVAs, with and without glucose variables from the exercise span as covariates, tested the integrated glucose-time areas for the effect of sex, time of day, and season. Exercise in the morning showed best recovery at all times of the year and females showed best recovery at each test time. In spite of significant time effects, a correlation between glucose recovery and amount of daylight could not be established. Significant differences in recovery between months, times of day and sexes were greatly influenced by glucose levels at start of the exercise, which showed a yearly rhythm.     

Association between selenium nutritional status and metabolic risk factors in men with visceral obesity

Background and aimPrevious evidence has suggested an association between selenium and cardiovascular disease, which is main outcome of metabolic syndrome. The aim of this study was to examine possible correlation between selenium nutritional status and metabolic risk factors in men with visceral obesity.MethodsPlasma samples were collected from 123 Indonesian men with visceral obesity. Their metabolic risk factors and selenium nutritional status were analyzed. The eligible subjects (n = 78) were stratified according to the International Diabetes Federation: obese, obese plus one component, and obese plus two components or more. Obese plus two components or more were diagnostic criteria of metabolic syndrome. Pearson's correlation was performed to examine the correlation in each group.ResultsIn the obese group, selenium positively correlated with high-density lipoprotein (HDL) cholesterol (r = 0.390, P < 0.05) and with fatty acid binding protein-4 (FABP4) (r = 0.474, P < 0.05); glutathione peroxidase-3 (GPx3) activity was inversely correlated with FABP4 (r = ?467, P < 0.05). In the obese plus one component group, GPx3 activity positively correlated with HDL cholesterol (r = 0.413, P < 0.05). In the metabolic syndrome group, selenium negatively correlated with monocytes chemoattractant protein (MCP)-1 (r = ?0.429, P < 0.05).ConclusionsThese results show that the association between selenium nutritional status and metabolic risk factors is limited to particular group of obese men with or without metabolic syndrome.     

Impact of global warming on viral diseases: what is the evidence?

Global warming is believed to induce a gradual climate change. Hence, it was predicted that tropical insects might expand their habitats thereby transmitting pathogens to humans. Although this concept is a conclusive presumption, clear evidence is still lacking--at least for viral diseases. Epidemiological data indicate that seasonality of many diseases is further influenced by strong single weather events, interannual climate phenomena, and anthropogenic factors. So far, emergence of new diseases was unlinked to global warming. Re-emergence and dispersion of diseases was correlated with translocation of pathogen-infected vectors or hosts. Coupled ocean/atmosphere circulations and 'global change' that also includes shifting of demographic, social, and economical conditions are important drivers of viral disease variability whereas global warming at best contributes.     

Proper orientation of the nicotinamide ring of NADP is important for the precatalytic conformational change in the 6-phosphogluconate dehydrogenase reaction

A recent study suggested sheep liver 6-phosphogluconate dehydrogenase (6PGDH) sees the oxidized and reduced cofactor differently [Cervellati, C., Dallocchio, F., Bergamini, C. M., and Cook, P. F. (2005) Biochemistry 44, 2432-2440]. Data were consistent with a rotation into the active site of the nicotinamide ring of NADP upon its reduction, resulting in a displacement of the 1-carboxylate of 3-keto-6PG better positioning it for decarboxylation, and further suggested a role of the cofactor in generating the precatalytic conformation of the enzyme. To further probe the role of the cofactor, multiple isotope effects were measured for the enzyme with mutations of the two residues that directly interact with the nicotinamide ring of NADP+, methionine 13 and glutamate 131. Kinetic and isotope effect data obtained in this study will thus be interpreted in terms of a mechanism that includes the rotation of the nicotinamide ring. The M13V, M13Q, M13C, and E131A mutant enzymes were characterized with respect to their kinetic parameters, deuterium, 13C, multiple deuterium/13C isotope effects, and the kinetics of utilization of 2-deoxy-6PG. Data suggest the position of the nicotinamide ring is important in identifying the open and closed conformations of the enzyme, with the latter optimal for catalysis. The 6PGDH reaction provides an excellent example of the use of substrate binding energy to drive catalysis.     

Intratypic recombination among lineages of type 1 vaccine-derived poliovirus emerging during chronic infection of an immunodeficient patient

We determined the complete genomic sequences of nine type 1 immunodeficient vaccine-derived poliovirus (iVDPV) isolates obtained over a 337-day period from a poliomyelitis patient from Taiwan with common variable immunodeficiency. The iVDPV isolates differed from the Sabin type 1 oral poliovirus vaccine (OPV) strain at 1.84% to 3.15% of total open reading frame positions and had diverged into at least five distinct lineages. Phylogenetic analysis suggested that the chronic infection was initiated by the fifth and last OPV dose, given 567 days before onset of paralysis, and that divergence of major lineages began very early in the chronic infection. Key determinants of attenuation in Sabin 1 had reverted in the iVDPV isolates, and representative isolates of each lineage showed increased neurovirulence for PVR-Tg21 transgenic mice. None of the isolates had retained the temperature-sensitive phenotype of Sabin 1. All isolates were antigenic variants of Sabin 1, having multiple amino acid substitutions within or near neutralizing antigenic sites 1, 2, and 3a. Antigenic divergence of the iVDPV variants from Sabin 1 followed two major independent evolutionary pathways. The emergence of distinct coreplicating lineages suggests that iVDPVs can replicate for many months at separate sites in the gastrointestinal tract. Some isolates had mosaic genome structures indicative of recombination across and within lineages. iVDPV excretion apparently ceased after 30 to 35 months of chronic infection. The appearance of a chronic VDPV excretor in a tropical, developing country has important implications for the strategy to stop OPV immunization after eradication of wild polioviruses.