Benzoquinones, a homoisoflavanone and other constitutents from Polygonatum alte-lobatum

From the rhizomes of Polygonatum alte-lobatum, two new homologous series of 1,4-benzoquinones, polygonaquinones A and B, a novel homoisoflavanone, a new gentrogenin glycoside and 13 known compounds were isolated and characterized. The structures of the new compounds were determined as two homologous series of three 2,5-dihydroxy-3-methyl-6-alkyl-1,4-benzoquinones and three 2-hydroxy-3-methyl-6-alkyl-1,4-benzoquinones, with chain lengths C21 to C23, and 4',5,7-trihydroxy-6,8-dimethylhomoisoflavanone and gentrogenin 3-O-beta-D-glucopyranosyl(1-->2)-[beta-D-xylopyranosyl(1-->3)] -beta-D-glucopyranosyl(1-->4)-beta-D-galactopyranoside.     

Plasminogen activator inhibitor-1 secretion of endothelial cells increases fibrinolytic resistance of an in vitro fibrin clot: evidence for a key role of endothelial cells in thrombolytic resistance

Time-dependent thrombolytic resistance is a critical problem in thrombolytic therapy for acute myocardial infarction. Platelets have been regarded as the main source of plasminogen activator inhibitor-1 (PAI-1) found in occlusive platelet-rich clots. However, endothelial cells are also known to influence the fibrinolytic capacity of blood vessels, but their ability to actively mediate time-dependent thrombolytic resistance has not been fully established. We will show that, in vitro, tumor necrosis factor-alpha-stimulated endothelial cells secrete large amounts of PAI-1 over a period of hours, which then binds to fibrin and protects the clot from tissue plasminogen activator-induced fibrinolysis. In vivo, endothelial cells covering atherosclerotic plaques are influenced by cytokines synthesized by plaque cells. Therefore, we propose that continuous activation of endothelial cells in atherosclerotic blood vessels, followed by elevated PAI-1 secretion and storage of active PAI-1 in the fibrin matrix, leads to clot stabilization. This scenario makes endothelial cells a major factor in time-dependent thrombolytic resistance.     

FOS is induced by singing in distinct neuronal populations in a motor network

The acute and subacute effects of intracerebroventricularly (ICV) administered nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) on locomotor activity were evaluated in awake adult rats. Immediately after ICV injection through an implanted cannula, locomotor activity was measured by a computerized system using infrared photocells, which allowed us to record locomotion, motility, and rearing simultaneously. A single dose of 5 microg mouse beta-NGF produced significant increases in horizontal ambulatory components of locomotor activity (locomotion and motility), but not vertical movement (rearing) 30-45 min after ICV administration. These increases lasted for at least 3-4 h. Systemic injection of 2.0 mg/kg mecamylamine, a central nicotinic receptor antagonist, inhibited the hyperactivity induced by NGF. Systemic injection of 0.5 mg/kg scopolamine, a muscarinic receptor antagonist, did not interfere with the NGF effects. Thus, while scopolamine induced marked increases in all three measures of behavior in both NGF and cytochrome-c-treated animals, locomotion and motility remained significantly higher in the NGF group. Immunohistochemistry demonstrated that NGF diffused readily from the ventricular space into brain parenchyma on the injected side and could be visualized 1 h after ICV injection. These results suggest that ICV administration of NGF increases locomotor activity by inducing acetylcholine release, and that nicotinic receptors are involved in the hyperactivity induced by NGF. ICV administration of 5 microg recombinant human BDNF had no significant effect on locomotor activity during the 0- to 4-h period after ICV injection. However, it produced significant decreases in locomotion, motility, and rearing 24-26 h later. Hence ICV administration of BDNF has entirely different effects on animal behavior from those evoked by NGF. While NGF elicits increases in ambulatory behavior within hours, BDNF causes delayed decreases in ambulatory behavior.     

The gene encoding human glutathione synthetase (GSS) maps to the long arm of chromosome 20 at band 11.2

Two forms of glutathione synthetase deficiency have been described. While one form is mild, causing hemolytic anemia, the other more severe form causes 5-oxo-prolinuria with secondary neurological involvement. Despite the existence of two deficiency phenotypes, Southern blots hybridized with a glutathione synthetase cDNA suggest that there is a single glutathione synthetase gene in the human genome. Analysis of somatic cell hybrids showed the human glutathione synthetase gene (GSS) to be located on chromosome 20, and this assignment has been refined to subband 20q11.2 using in situ hybridization.     

IEEE standard 802.16: a technical overview of theWirelessMANTM air interface for broadband wirelessaccess

The broadband wireless access industry, which provides high-rate network connections to stationary sites, has matured to the point at which it now has a standard for second-generation wireless metropolitan area networks. The IEEE standard 802.16, with its WirelessMAN^TM air interface, sets the stage for widespread and effective deployments worldwide. This article overviews the technical medium access control and physical layer features of this new standard     

Influence of DNA repair by ada and ogt alkyltransferases on the mutational specificity of alkylating agents

We investigated the influence of the alkyltransferases (ATases) encoded by the ada and ogt genes of Escherichia coli on the mutational specificity of alkylating agents. A new mutational assay for selection of supF- mutations in shuttle-vector plasmids was used. Treating plasmid-bearing bacteria with N-methyl-N-nitrosourea (MNU), N-ethyl-N-nitrosourea (ENU), and ethyl methanesulfonate (EMS) dramatically increased the mutation frequency (from 33-fold to 789-fold). The vast majority of mutations (89-100%) were G:C-->A:T transitions. This type of mutation increased in ada- (MNU) or ogt- (ENU) bacteria, suggesting that repair of O6-methylguanine by ada ATase and repair of O6-ethylguanine by ogt ATase contribute mainly to the decrease in G:C-->A:T transitions. The analysis of neighboring base sequences revealed an overabundance of G:C-->A:T transitions at 5'-GG sequences. The 5'-PuG bias increased in ATase-defective cells, suggesting that these sequences were not refractory to repair. G:C-->A:T transitions occurred preferentially in the untranscribed strand after in vivo exposure. That this strand specificity was detected even in bacteria devoid of ATase activity (ada- ogt-) and not after in vitro mutagenesis suggests a bias for damage induction rather than for DNA repair. Highly significant differences were found between the in vivo and in vitro incidences of G:C-->A:T substitutions at the two major hotspots, positions 123 (5'-GGG-3'; antisense strand) and 168 (5'-GGA-3'; sense strand). These results are explained by differences in the probability of formation of stem-loop structures in vivo and in vitro.