Antinociceptive and Met-enkephalin releasing effects of tachykinins and substance P fragments

Substance P (SP), physalaemin, SP4-11, SP5-11 and the SP5-11 analog DiMe-C7 induce an antinociceptive effect in rats after intraventricular administration. Other tachykinins and the N-terminal fragments of SP are inactive. All antinociceptive peptides increase the Met-enkephalin efflux from slices of rat periaqueductal gray matter and their antinociceptive potency is correlated with their capacity to release Met-enkephalin. The results, discussed in the light of current theories on different tachykinin receptors, suggest that the SP-P receptor subtype may be involved in the control of noxious stimulation elicited by SP at supraspinal levels.     

Concomitant regulation of hippocampal calcium antagonist receptors and calcium uptake by substance P

The interaction of various neuropeptides with calcium antagonist binding was investigated in rat hippocampus. Among the peptides examined Substance P selectively increased the binding of phenylalkylamine and dihydropyridine calcium antagonists; this action was receptor mediated. No effect was observed with Substance P in other brain areas and with neurotensin and met-enkephalin in all the areas examined. The modification in calcium antagonist binding is functionally paralleled by an area specific increase in voltage-dependent calcium uptake. These data suggest that in hippocampus Substance P may be an endogenous regulator of voltage sensitive calcium channels.     

Sleep-related hippocampo-cortical interplay during emotional memory recollection

Emotional events are usually better remembered than neutral ones. This effect is mediated in part by a modulation of the hippocampus by the amygdala. Sleep plays a role in the consolidation of declarative memory. We examined the impact of sleep and lack of sleep on the consolidation of emotional (negative and positive) memories at the macroscopic systems level. Using functional MRI (fMRI), we compared the neural correlates of successful recollection by humans of emotional and neutral stimuli, 72 h after encoding, with or without total sleep deprivation during the first post-encoding night. In contrast to recollection of neutral and positive stimuli, which was deteriorated by sleep deprivation, similar recollection levels were achieved for negative stimuli in both groups. Successful recollection of emotional stimuli elicited larger responses in the hippocampus and various cortical areas, including the medial prefrontal cortex, in the sleep group than in the sleep deprived group. This effect was consistent across subjects for negative items but depended linearly on individual memory performance for positive items. In addition, the hippocampus and medial prefrontal cortex were functionally more connected during recollection of either negative or positive than neutral items, and more so in sleeping than in sleep-deprived subjects. In the sleep-deprived group, recollection of negative items elicited larger responses in the amygdala and an occipital area than in the sleep group. In contrast, no such difference in brain responses between groups was associated with recollection of positive stimuli. The results suggest that the emotional significance of memories influences their sleep-dependent systems-level consolidation. The recruitment of hippocampo-neocortical networks during recollection is enhanced after sleep and is hindered by sleep deprivation. After sleep deprivation, recollection of negative, potentially dangerous, memories recruits an alternate amygdalo-cortical network, which would keep track of emotional information despite sleep deprivation.     

Helicobacter pylori, T cells and cytokines: the "dangerous liaisons"

Helicobacter pylori infection is the major cause of gastroduodenal pathologies, but only a minority of infected patients develop chronic and life threatening diseases, as peptic ulcer, gastric cancer, B-cell lymphoma, or autoimmune gastritis. The type of host immune response against H. pylori is crucial for the outcome of the infection. A predominant H. pylori-specific Th1 response, characterized by high IFN-gamma, TNF-alpha, and IL-12 production associates with peptic ulcer, whereas combined secretion of both Th1 and Th2 cytokines are present in uncomplicated gastritis. Gastric T cells from MALT lymphoma exhibit abnormal help for autologous B-cell proliferation and reduced perforin- and Fas-Fas ligand-mediated killing of B cells. In H. pylori-infected patients with autoimmune gastritis cytolytic T cells infiltrating the gastric mucosa cross-recognize different epitopes of H. pylori proteins and H+K+ ATPase autoantigen. These data suggest that peptic ulcer can be regarded as a Th1-driven immunopathological response to some H. pylori antigens, whereas deregulated and exhaustive H. pylori-induced T cell-dependent B-cell activation can support the onset of low-grade B-cell lymphoma. Alternatively, H. pylori infection may lead in some individuals to gastric autoimmunity via molecular mimicry.     

Viral fusion peptides and identification of membrane-interacting segments

Viral envelope glycoproteins promote infection by mediating fusion between viral and cellular membranes. Fusion occurs after dramatic conformational changes within fusion proteins, leading to the exposure of a short stretch of mostly apolar residues, termed the fusion peptide, which is presumed to insert into the membrane and initiate the fusion process. The typical global composition of fusion peptides, rich in hydrophobic but also in small amino acids such as alanine and glycine, was used here as bait to detect other peptidic segments that can insert into membranes. We so evidenced a similar composition in several cytotoxic peptides, which promote pore formation such as peptides involved in amyloidoses and hydrophobic alpha-hairpins of pore-forming toxins. It is suggested that the structural plasticity observed for several membrane active peptides can be conferred by this particular global amino acid composition, which could be thus used to predict such functional behavior from genome data.     

Promotion of uniparental inheritance of mitochondrial drug resistance by delayed division of yeast zygotes

Summary Uniparental inheritance of mitochondrial markers conferring resistance to 3 (3,4-dichlorphenyl)-1,1-dimethylurea (diuron or DCMU) and antimycin in the fission yeast Schizosaccharomyces pombe is promoted by delaying first division of zygotes.     

Hydrolysis of cyclosporin A: Identification of 1,11 seco-cyclosporin A and 4,5 secoisoCyclosporin A by FAB-MS/MS

We have previously reported that treatment of CsA with aqueous HCl gives rise to the formation of a number of water-soluble compounds. Two of these were identified from their FAB-MS/MS spectra as open-chain nona- and decapeptides. We describe here the identification of two other main compounds deriving from the same treatment. Identification was rendered possible from the comparison of their FAB-MS/MS spectra with those of methyl and acetyl derivatives. The two compounds are water-soluble, open-chain undecapeptides corresponding to 1,11 seco-CsA and of 4,5 seco-isoCsA, respectively.     

The phenology of sexual reproduction inGinkgo biloba: Ecological and evolutionary implications

This study examines how the latitude of cultivation ofGinkgo biloba affects the timing of all phases of its sexual reproductive cycle, from pollination through germination. Seeds produced by trees growing in warm-temperate climates germinate earlier in the year than seeds produced in cold-temperate climates, and they have a longer period of time available for seedling establishment. The embryos ofG. biloba seeds possess a temperature-dependent developmental-delay mechanism that allows seeds to survive winter by preventing premature germination in the fall. This and other cold-climate adaptations appear to have evolved within the genusGinkgo during the early Cretaceous, when the Northern Hemisphere was undergoing dramatic cooling after a long period of stable, warm conditions.Ginkgo biloba seeds possess an odoriferous sarcotesta that attracts mammalian scavengers in Asia-most notably members of the Carnivora—presumably by mimicking the smell of carrion. Seeds cleaned of their sarcotesta germinated faster and at higher percentages than those with their sarcotesta intact, suggesting that animal dispersal plays an important role in promoting seedling establishment. During the Cretaceous, potential dispersal agents included mammals, birds, and carnivorous dinosaurs.     

Preliminary study of the physical chemistry and catalytic properties of glutathione-S-transferase from human placenta

Glutathione-S-transferase activity has been identified in the cytosol of human placenta. The specific activity measured is about 50% of that found in human liver. While some kinetic data have a close correspondence with those attributed to transferases of other sources, the molecular weight (60.000 daltons) and electric properties of this protein are unusual. The inhibitory effect of several non-substrate compounds suggests that also the placental Glutathione-S-transferase may play some role in detoxication of exogenous substances.     

Evaluation of various hemorheological parameters in nonagenarians: evidence of an increase of fibrinogen

Cardiovascular disease is the most frequent cause of mortality in the elderly. A reduced microvascular blood flow associated with an increase in atherosclerosis might contribute to age related increases in the incidence of ischemic vascular disease. In order to evaluate the effect of age on some haemorheological parameters, blood and plasma viscosity and fibrinogen have been measured in 10 healthy elderly subjects, aged between 88 and 96 years, compared with 15 healthy young subjects (mean age 37 years). Elderly subjects showed a significant increase in plasma fibrinogen (p less than 0.0005) and a trend to an increase in plasma viscosity, whereas no difference was present in blood viscosity. These data confirm that aging is associated with a greater deal of thrombotic risk factors, the most important of which seems to be fibrinogen.