The role of survivin in angiogenesis during zebrafish embryonic development

Background  

Survivin is the smallest member of the inhibitor of apoptosis (IAP) gene family. Recently, the zebrafish survivin-1 gene has been cloned, showing remarkable sequence identity and similarity over the BIR domain compared with human and mouse survivin gene. Here we investigated the role of survivin in angiogenesis during zebrafish development. Morpholinos (MOs) targeting the 5' untranslated region (UTR) (Sur_UTR) and sequences flanking the initiation codon (Sur_ATG) of zebrafish survivin-1 gene were injected into embryos at 1–4 cell stage. Vasculature was examined by microangiography and GFP expression in Tg(fli1:EGFP) ^y1 embryos. Results: In embryos co-injected with Sur_UTR and Sur_ATG-MOs, vasculogenesis was intact but angiogenesis was markedly perturbed, especially in the inter-segmental vessels (ISV) and dorsal longitudinal anastomotic vessels (DLAV) of the trunk, the inner optic circle and optic veins of developing eyes and the sub-intestinal vessels. Apoptosis was increased, as shown by TUNEL staining and increase in caspase-3 activity. Efficacy of Sur_UTR and Sur_ATG-MOs was demonstrated by translation inhibition of co-injected 5'UTR survivin:GFP plasmids. The phenotypes could be recapitulated by splice-site MO targeting the exon2-intron junction of survivin gene and rescued by survivin mRNA. Injection of human vascular endothelial growth factor (VEGF) protein induced ectopic angiogenesis and increased survivin expression, whereas treatment with a VEGF receptor inhibitor markedly reduced angiogenesis and suppressed survivin expression. Conclusion: Survivin is involved in angiogenesis during zebrafish development and may be under VEGF regulation.     

Theoretical analysis on relationship between the neural activity and the EEG

Firstly, a collective oscillation mode of the neural activity is derived from the neural network system by using the multicompartment equation and the projection operator technique. This technique takes into account higher order interactions among neurons. The solution of the equation gives a chain structure with an infinite number of circuit loops in which each of them is only composed of four neurons. The obtained eigenvalues are quite similar to the spectrum of frequencies of the EEG. Secondly, the time-dependent behavior of the observed EEG is simulated by starting from the elementary process of action potential trains of neurons, which includes the effect of the collective oscillation mode mentioned above. This gives a comprehensive derivation of the EEG from the neural activity of action potentials. The simulation assumes that information of the action potential trains can be transmitted to the EEG through the intermediate states of the postsynaptic potential trains and the slow waves. The paper reports that a slightly modulated activity of a relatively small amount of neurons can cause a strong influence on the shape of the global EEG and that the calculated results reproduce the characteristic features of the EEG in a rat such as the theta rhythm, the spindle wave and the arousal wave.     

Movements by juvenile and immature Steller's Sea Eagles Haliaeetus pelagicus tracked by satellite

Twenty‐four juvenile Steller's Sea Eagles Haliaeetus pelagicus were tracked via satellite from natal areas in Magadan, Kabarovsk, Amur, Sakhalin and Kamchatka. Nestling dispersal occurred between 9 September and 6 December (n = 24), mostly 14 September–21 October, and did not differ among regions or years. Most eagles made stopovers of 4–28 days during migration. Migration occurred 9 September–18 January, mostly along previously described routes, taking 4–116 days to complete (n = 18). Eagles averaged 47.8 km/day excluding stopovers; 22.9 km/day including stopovers. The mean degrees of latitude spanned during migration was: Kamchatka, 2.1; Magadan, 11.6; Amur, 7.3; and Sakhalin, 1.1. Eagle winter range sizes varied. Eagles concentrated in 1–3 subareas within overall winter ranges. The mean size of the first wintering subareas was 274 km², the second 529 km², and the third 1181 km². Second wintering areas were south of first wintering areas. Spring migration started between 2 February and 31 March. Two eagles from Magadan were tracked onto summering grounds, well south of their natal areas. Both had early and late summering areas. One bird was followed for 25 months. It initiated its second autumn migration in the first half of October and arrived on its wintering grounds on 26 December. The second autumn migration covered 1839 km (20.9–22.4 km/day). Unlike its first winter when it used two subareas, this bird used only one subarea in 1998–99, but this was located near wintering areas used in 1997–98. It left its wintering ground between 13 April and 13 May, and arrived on its summering grounds between 7 June and 8 July. Unlike most satellite radiotracking studies, data are presented from a relatively large number of birds from across their breeding range, including new information on eagle movements on the wintering grounds and during the second year.     

Water-soluble lipoproteins from yolk granules in sea urchin eggs. II. Chemical composition.

The chemical composition of yolk lipoproteins (YLP-1, 2, and 3) was determined. YLP-1, 2, and 3 were quite similar as regards the chemical composition of lipids, proteins, and carbohydrate moieties. Each lipoprotein has an average dry weight composition of lipids (55--72%) and apo-lipoproteins (28--45%) containing protein, hexose, hexosamine, and sialic acid. In each lipoprotein, triacylglycerol is a major lipid component (70--83%), followed by phospholipid (8--16%), cholesterol (free and esterified, 8--10%), and free fatty acid (3--4%). Phosphatidylcholine and phosphatidylserine account for 68--74% and 16--24% of the phospholipids, respectively. The fatty acid compositions of total lipids from each lipoprotein are quite similar, with a high degree of unsaturation (63--65%). The carbohydrate content of apolipoprotiens from each lipoprotein is remarkably high (27--31% of apo-lipoproteins) and their composition is very simple: mannose and glucosamine are major constituents in the polysaccharide moiety of each lipoprotein and sialic acid is all in the N-glycolyl form. The amino acid compositions of apo-lipoproteins are quite similar in YLP-1, 2, and 3, with high contents of aspartic acid, glutamic acid, threonine, serine, and leucine. Furthermore, a small amount of glycolipids is present in the yolk lipoproteins. They were separated into six components on TLC. All of them are resorcinol-positive, indicating the presence of sialoglycolipids.     

Postnatal development of galanin-like peptide mRNA expression in rat hypothalamus

We examined the developmental change of GALP mRNA in male and female rat hypothalamus during postnatal day 1 to 60, using in situ hybridization histochemistry. Neuropeptide Y (NPY) and proopiomelanocortin (POMC) mRNA in the hypothalamus were also examined because they are important in the regulation of food intake. GALP mRNA was first detected in the arcuate nucleus (ARC) on day 8. GALP mRNA was gradually increased between day 8 and 14 and markedly increased between day 14 and 40, which is the weaning and pubertal period in rats. After day 40, there were no significant differences in GALP mRNA. In contrast to GALP, NPY and POMC mRNAs were detected in the ARC from day 1 and lasted to day 60. There was no sexual dimorphism in GALP, NPY and POMC mRNAs during postnatal development. Next, we examined the effect of the milk deprivation for 24 h on GALP, NPY and POMC mRNA in pups. GALP mRNA did not change by milk deprivation on day 9 and 15, while milk deprivation had a significant effect on NPY and POMC mRNA on day 15. These results suggest that the development of GALP may be associated with developmental changes such as weaning, feeding and maturation of reproductive functions. The regulatory mechanism of GALP mRNA is different from that of the NPY and POMC genes during postnatal development.     

Strongyloides venezuelensis: the antigenic identity of eight strains for the immunodiagnosis of human strongyloidiasis

The antigens of eight strains of Strongyloides venezuelensis were identified by means of the indirect immunofluorescence antibody (IFAT), enzyme-linked immunosorbent assay (ELISA) and immunoblot (IB) tests. Infective larvae (L3) from these strains were obtained from Rattus norvegicus feces cultures. For IFAT, sections of L3 were used while the ELISA and IB, tests were conducted with alkaline extract. Ninety serum samples were tested: 30 from patients with S. stercoralis, 30 from patients with other parasitic diseases, and 30 from healthy subjects (free of parasites). Average sensitivity and specificity among all eight strains, both for IFAT and ELISA, were, respectively, 93% and 100%. In the IB, anti-S. stercoralis IgG recognized a single antigenic fraction with 45 kDa. Serum samples from patients with S. stercoralis revealed antigens from different strains of S. venezuelensis, indicating antigenic identity for possible use in the synthesis of recombinant antigen that could be useful in immunodiagnosis and vaccine against this parasite.     

Adrenomedullin in the cerebral circulation.

The central nervous system requires an effective autoregulation of cerebral circulation in order to meet the critical and unusual demands of the brain. In addition, cerebral microvessels has a unique feature, the formation of the blood-brain barrier, which contributes to the stability of the brain parenchymal microenvironment. Many factors are known to be involved in the regulation of cerebral circulation and blood-brain barrier functions. In the last few years a new potential candidate, adrenomedullin, a hypotensive peptide was added to this list. Adrenomedullin has a potent vasodilator effect on the cerebral vasculature, and it may be implicated in the pathologic mechanism of cerebrovascular diseases. In this review, we describe current knowledge about the origin and possible role of adrenomedullin in the regulation of cerebral circulation and blood-brain barrier functions.     

Leukotrienes play a role in the control of parasite burden in murine strongyloidiasis

It is clear that leukotrienes mediate inflammatory response; new aspects of leukotriene function have recently been described. In this study, we demonstrate that leukotrienes are key chemical mediators in the control of parasite burdens in mice infected with Strongyloides venezuelensis. High leukotriene levels were detected in the lungs and small intestines of Swiss mice. In infected Swiss mice treated with MK886, a leukotriene synthesis inhibitor, numbers of adult worms, and eggs/g/feces were greater than in infected-only animals. The MK886 treatment inhibited leukotriene B(4) production in the lungs and small intestines, albeit on different postinfection days. Similarly, parasite burdens and eggs/g/feces were greater in 5-lipoxygenase(-/-) mice than in wild-type animals. These observation were confirmed by histopathological study of the duodena. We subsequently observed significant lower numbers of eosinophils and mononuclear cells in the blood, peritoneal cavity fluid, and bronchoalveolar lavage fluid of Swiss mice treated with MK886. In the lung parenchyma of infected animals, MK886 significantly inhibited synthesis of IL-5 at the beginning of infection, whereas levels of IL-12 increased progressively throughout the postinfection period. However, levels of leukotriene C(4), PGE(2), TNF-alpha, IL-3, IL-4, IFN-gamma, and IL-10 were comparable between the treated and untreated groups. Nevertheless, IgE and IgG1 (but not IgG2a) synthesis was also significantly inhibited by MK886 administration. Therefore, in S. venezuelensis-infected mice, adult worm and egg burdens are leukotriene dependent. These findings indicate potential immunostimulatory strategies involving leukotriene administration, and may serve as an alert to physicians treating Strongyloides stercoralis-infected patients presenting asthma-like symptoms because use of 5-lipoxygenase inhibitors may worsen the infection.