Alterations of Choroidal Blood Flow Regulation in Young Healthy Subjects with Complement Factor H Polymorphism

A common polymorphism in the complement factor H gene (rs1061170, Y402H) is associated with a high risk of age-related macular degeneration (AMD). In the present study we hypothesized that healthy young subjects homozygous for the high-risk haplotype (CC) show abnormal choroidal blood flow (ChBF) regulation decades before potentially developing the disease. A total of 100 healthy young subjects were included in the present study, of which 4 subjects were excluded due to problems with genotyping or blood flow measurements. ChBF was measured continuously using laser Doppler flowmetry while the subjects performed isometric exercise (squatting) for 6 minutes. The increase in ChBF was less pronounced than the response in ocular perfusion pressure (OPP), indicating for some degree of choroidal blood flow regulation. Eighteen subjects were homozygous for C, 47 subjects were homozygous for T and 31 subjects were heterozygous (CT). The increase in OPP during isometric exercise was not different between groups. By contrast the increase in ChBF was more pronounced in subjects homozygous for the high risk C allele (p = 0.041). This was also evident from the pressure/flow relationship, where the increase in ChBF in homozygous C carriers started at lower OPPs as compared to the other groups. Our data indicate that the regulation of ChBF is abnormal in rs1061170 CC carriers. So far this polymorphism has been linked to age related macular degeneration (AMD) mainly via inflammatory pathways associated with the complement system dysfunction. Our results indicate that it could also be related to vascular factors that have been implicated in AMD pathogenesis.     

Maternal Transfer and Protective Role of the Alternative Complement Components in Zebrafish Danio rerio

Embryos of most fish develop externally and are exposed to an aquatic environment full of potential pathogens, whereas they have little or only limited ability to mount an efficient and protective response. How fish embryos survive pathogenic attacks remains poorly defined. Here we demonstrate that the maternal immunization of female zebrafish with formalin-killed Aeromonas hydrophila causes a significant increase in C3 and Bf contents in the mother, a corresponding rise in the offspring, and induces a remarkable increase in the hemolytic activities in both the mother and offspring. In addition, the embryos derived from the immunized mother are significantly more tolerant to A. hydrophila challenge than those from the unimmunized fish, and blocking C3 and Bf activities by injection of the antibodies against C3 and Bf into the embryos render them more susceptible to A. hydrophila. These results clearly show that the protection of zebrafish embryos against A. hydrophila can be achieved by the maternally-transferred immunity of the complement system operating via the alternative pathway. This appears to be the first report providing in vivo evidences for the protective role of the alternative complement components in the early embryos of zebrafish, paving the way for insights into the in vivo function of other maternally-transferred factors in fish.     

Effects of lateral amygdala lesions on the responses to novelty in mice

Bilateral electrolytic lesions restricted to the lateral, basolateral and basomedial amygdaloid nuclei in mice produced a lack of avoidance responses towards novel stimuli. While controls showed avoidance and burying reactions to a novel object introduced into their familiar environment, lesioned mice displayed a high number of approach responses and a low level of burying reactions. Furthermore, when given the opportunity to move around freely in simultaneously presented novel and familiar places, control mice at first exhibited avoidance reactions to the novel environment before showing novelty preference. There were no avoidance reactions in lesioned mice. These data are consistent with the hypothesis that amygdala plays a specific role in the regulation of defensive reactions.     

Regulation of the amylase secretion by the yeast Filobasidium capsuligenum and a 2-deoxy-d-glucose resistant mutant

Summary The regulation of extracellular amylase production by the basidiomycetous yeast Filobasidium capsuligenum CCY 64-5-1 was characterized using growing and resting cells. A basal level of amylolytic activity was produced with various carbon sources including glucose. Amylase secretion was repressed by glucose and, more severely, by 2-deoxy-d-glucose, whereas compounds with -1,4-linked glucose, such as methyl glucoside, maltose, -cyclodextrin and soluble starch, served as inducers. Repression was not relieved by exogenously added cAMP. The effects of several metabolic inhibitors on amylase secretion were studied. Following UV-mutagenesis a mutant strain (FC-5) capable of growing in a 2-deoxy-d-glucose supplemented corn starch medium was selected for further characterization. This strain produced more amylase, had acquired an increased resistance against repression by glucose, and retained a growth rate comparable to the wild type. FC-5 was also characterized by a reduced glucokinase activity and an increased hexokinase activity.     

Characterization of the Erwinia carotovora pelB gene and its product pectate lyase.

The pelB gene encodes pectate lyase B, one of three pectate lyases identified in Erwinia carotovora EC. Pectate lyase B was purified from Escherichia coli containing the pelB gene on a recombinant plasmid. The activity of the protein was optimal at a pH of 8.3. The amino acid composition, N-terminal amino acid sequence, and C-terminal peptide sequence were determined and compared with the polypeptide sequence deduced from the DNA sequence of pelB. Purified pectate lyase B started at amino acid 23 of the predicted sequence, suggesting that a 22-amino-acid leader peptide had been removed. Pectate lyase B of E. carotovora EC and pectate lyase B of E. chrysanthemi EC16 contain 352 and 353 amino acids, respectively (N. T. Keen, S. Tanaki, W. Belser, D. Dahlbeck, and B. Staskawicz, J. Bacteriol. 168:595-606, 1986). The two proteins are 72% homologous on the basis of DNA sequence data, and 75% of the amino acids are identical.