Venom-Sweet-Venom: N-Linked Glycosylation in Snake Venom Toxins

Protein glycosylation represents one of the most important post-translational events, and is a mean of diversifying a protein without recourse to the genome. The venoms produced by snakes contain an abundance of glycoproteins with N-linked carbohydrates. N-linked glycosylation can ensure the correct folding of important functional domains. Characterization of carbohydrates structures aids in development of human therapeutics by snake venom toxins.

Evaluation of Leptospiral Recombinant Antigens MPL17 and MPL21 for Serological Diagnosis of Leptospirosis by Enzyme-Linked Immunosorbent Assays

Leptospirosis is a zoonosis of multisystem involvement caused by pathogenic strains of the genus Leptospira. In the last few years, intensive studies aimed at the development of a vaccine have provided important knowledge about the nature of the immunological mechanisms of the host. The purpose of this study was to analyze the immune responses to two recombinant proteins, MPL17 and MPL21 (encoded by the genes LIC10765 and LIC13131, respectively) of Leptospira interrogans serovar Copenhageni in individuals during infection. The recombinant proteins were expressed in Escherichia coli as six-His tag fusion proteins and were purified from the soluble bacterial fraction by affinity chromatography with Ni2+ -charged resin. The recombinant proteins were used to evaluate their ability to bind to immunoglobulin G (IgG) (and IgG subclass) or IgM antibodies in serum samples from patients in the early and convalescent phases of leptospirosis (n = 52) by enzyme-linked immunosorbent assays. The prevalences of total IgG antibodies against MPL17 and MPL21 were 38.5% and 21.2%, respectively. The titers achieved with MPL17 were statistically significantly higher than those obtained by the reference microscopic agglutination test. The specificity of the assay was estimated to be 95.5% for MPL17 and 80.6% for MPL21 when serum samples from individuals with unrelated febrile diseases and control healthy donors were tested. The proteins are conserved among Leptospira strains that cause human and animal diseases. MPL17 and MPL21 are most likely new surface proteins of leptospires, as revealed by liquid-phase immunofluorescence assays with living organisms. Our results demonstrate that these recombinant proteins are highly immunogenic and, when they are used together, might be useful as a means of diagnosing leptospirosis.

Public attitudes to the use of wildlife by Aboriginal Australians: Marketing of wildlife and its conservation

Indigenous Australians have socioeconomic attributes similar to those of residents in some developing countries. Their utilisation of wildlife could add to their economic opportunities. Attitudes of a sample of the Australian public towards the subsistence use of wildlife by Indigenous Australians and whether or not they should be allowed to sell wildlife and wildlife products are examined. Allowing such possibilities could provide economic incentives for nature conservation among local people. We explore whether those sampled believe that Indigenous Australians should do more than other groups and institutions to conserve Australia's tropical species, and whether or not they should be allowed to take common as well as endangered wildlife species for food. Attitudes of the sampled public towards Indigenous Australians earning income from trophy hunting and from the harvesting of northern long-necked turtles for the pet trade are canvassed. The possible conservation consequences of sale of wildlife by Indigenous Australians are discussed.

Functional polymorphisms in the promoter of the matrix metalloproteinase-9 (MMP-9) gene are not linked with significant plasma MMP-9 variations in healthy subjects

Background: Matrix metalloproteinase-9 (MMP-9) is involved in the degradation of the extracellular matrix during physiological and pathological processes. Two functional polymorphisms [C(-1562)T and microsatellite (CA)(13-25)] in the promoter region of the MMP-9 gene have been associated with several diseases. The aim of this study was to examine whether these MMP-9 polymorphisms and haplotypes are linked with plasma MMP-9 variations in healthy subjects. Methods: We studied 177 healthy male white volunteers (age range 20-55 years) who were non-smokers and not taking any medication. Genomic DNA was extracted from whole blood and genotypes for the C(-1562)T and the microsatellite (CA)(n) polymorphisms were determined. MMP-9 levels were measured in plasma samples by gelatin zymography. Results: The frequency of the alleles C and T for the C(-1562)T polymorphism were 90% and 10%, respectively. The frequency of the alleles with less than 21 CA repeats Q and with 21 repeats or higher (H) were 47% and 53%, respectively. We found no differences in plasma MMP-9 levels among the genotype groups or among different haplotypes (all p > 0.05). Conclusions: These findings suggest that functional polymorphisms in the promoter of the MMP-9 gene are not linked with significant plasma MMP-9 variations in healthy subjects.

Height discordance in monozygotic females is not attributable to discordant inactivation of X-linked stature determining genes

We tested the hypothesis that X-linked genes determining stature which are subject to skewed or non-random X-inactivation can account for discordance in height in monozygotic female twins. Height discordant female monozygotic adult twins (20 pairs) were identified from the Australian Twin Registry, employing the selection criteria of proven monozygosity and a measured height discordance of at least 5 cm. Differential X-inactivation was examined in genomic DNA extracted from peripheral lymphocytes by estimating differential methylation of alleles at the polymorphic CAG triplet repeat of the Androgen receptor gene (XAR). There were 17/20 MZ pairs heterozygous at this locus and informative for analysis. Of these, 10/17 both had random X-inactivation, 5/17 showed identical X-inactivation patterns of non random inactivation and 2/17 (12%) showed discordant X-inactivation. There was no relationship between inactivation patterns and self-report chorionicity. We conclude that non-random X-inactivation does not appear to be a major contributor to intra-pair height discordance in female MZ twins.

Health services research using linked records: who consents and what is the gain?

Objective: To assess consent to record linkage, describe the characteristics of consenters and compare self-report versus Medicare records of general practitioner use. Method. Almost 40,000 women in the Australian Longitudinal Study on Women's Health were sent a request by mail for permission to link their Medicare records and survey data. Results: 19,700 women consented: 37% of young (18-23 years), 59% of mid-age (4550 years) and 53% of older women (70-75 years). Consenters tended to have higher levels of education and, among the older cohort, were in better health than nonconsenters. Women tended to under-report the number of visits to general practitioners. Conclusions: Record linkage of survey and Medicare data on a large scale is feasible. The linked data provide information on health and socio-economic status which are valuable for understanding health service utilisation. Implications: Linked records provide a powerful tool for health care research, particularly in longitudinal studies.

Human twinning is not linked to the region of chromosome 4 syntenic with the sheep twinning gene FecB

The tendency to dizygotic (DZ) twinning is inherited in both humans and sheep, and a fecundity gene in sheep (FecB) maps to sheep chromosome 6, syntenic with human 4q21-25. Our aim was to see whether a gene predisposing to human DZ twinning mapped to this region. DNA was collected from 169 pairs and 17 sets of 3 sisters (trios) from Australia and New Zealand who had each had spontaneous DZ twins, mostly before the age of 35, and from a replication sample of 111 families (92 affected sister pairs) from The Netherlands. Exclusion mapping was carried out after typing 26 markers on chromosome 4, of which 8 spanned the region Likely to contain the human homologue of the sheep FecB gene. We used nonparametric affected sib pair methods for linkage analysis [ASPEX 2.2, Hinds and Risch, 1999]. Complete exclusion of linkage (lod < -2) of a gene conferring a relative risk for sibs as low as 1.5 ((s) > 1.5) was obtained for all but the p terminus region on chromosome 4. Exclusion in the syntenic region was stronger, down to lambda (s) = 1.3. We concluded that if there is a gene influencing DZ twinning on chromosome 4, its effect must be minor. (C) 2001 Wiley-Liss, Inc.

X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy

To determine whether human X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome (IPEX; MIM 304930) is the genetic equivalent of the scurfy (sf) mouse, we sequenced the human ortholog (FOXP3) of the gene mutated in scurfy mice (Foxp3), in IPEX patients. We found four non-polymorphic mutations. Each mutation affects the forkhead/winged-helix domain of the scurfin protein, indicating that the mutations may disrupt critical DNA interactions.