NEUROPEPTIDE-F - A NOVEL PARASITIC FLATWORM REGULATORY PEPTIDE FROM MONIEZIA-EXPANSA (CESTODA, CYCLOPHYLLIDEA)

Using a C-terminally directed pancreatic polypeptide (PP) antiserum and immunocytochemical methods, PP-immunoreactivity (IR) was localized throughout the central (CNS) and peripheral nervous systems (PNS) of the cestode, Moniezia expansa. In the CNS, immunostaining was evident in the paired cerebral ganglia (primitive brain), connecting commissure, and the paired longitudinal nerve cords that are cross-linked by numerous regular transverse connectives. The PNS was seen to consist of a fine anastomosing nerve-net of immunoreactive fibres, many of which were closely associated with reproductive structures. Radioimmunoassay of this peptide IR in acid-alcohol extracts of the worm measured 192.8 ng/g of PP-IR. HPLC analyses of the M. expansa PP-IR identified a single molecular form which was purified to homogeneity. Plasma desorption mass spectrometry (PDMS) of purified parasite peptide resolved a single peptide with a molecular mass of 4599 +/- 10 Da. Automated gas-phase Edman degradation identified a 39-amino acid peptide with a C-terminal phenylalaninamide. Examination of its primary structure shows that it displays significant sequence homology with the vertebrate neuropeptide Y superfamily, suggesting that this platyhelminth-derived peptide is the phylogenetic precursor. Neuropeptide F (M. expansa) is the first regulatory peptide to be fully sequenced from the phylum Platyhelminthes and may represent a member of an important new class of invertebrate neuropeptide.

Comparison of the binding specificity of two bacterial metalloproteases, LasB of Pseudomonas aeruginosa and ZapA of Proteus mirabilis, using N-alpha mercaptoamide template-based inhibitor analogues

The metalloproteases ZapA of Proteus mirabilis and LasB of Pseudomonas aeruginosa are known to be virulence factors their respective opportunistic bacterial pathogens, and are members of the structurally related serralysin and thermolysin families of bacterial metalloproteases respectively. Secreted at the site of infection, these proteases play a key role in the infection process, contributing to tissue destruction and processing of components of the host immune system. Inhibition of these virulence factors may therefore represent an antimicrobial strategy, attenuating the virulence of the infecting pathogen. Previously we have screened a library of N-alpha mercaptoamide dipeptide inhibitors against both ZapA and LasB, with the aim of mapping the S1' binding site of the enzymes, revealing both striking similarities and important differences in their binding preferences. Here we report the design, synthesis, and screening of several inhibitor analogues, based on two parent inhibitors from the original library. The results have allowed for further characterization of the ZapA and LasB active site binding pockets, and have highlighted the possibility for development of broad-spectrum bacterial protease inhibitors, effective against enzymes of the thermolysin and serralysin metalloprotease families.

An ecotoxicological approach to assessing the impact of tanning industry effluent on river health

A study was conducted to investigate the sediment health and water quality of the River Sagana, Kenya, as impacted by the local tanning industry. Chemical analysis identified the main chemical pollutants (pentachlorophenols and chromium) while a bioassay addressed pollutant bioavailability. The bioassay, exploiting the luminescence response of a lux marked bacterial biosensor, was coupled to a dehydrogenase and Dapnia magna test to determine toxicity effects on sediments. Results highlighted the toxicity of the tannery effluent to the sediments at the point of discharge (64% of control bioluminescence) with gradual improvement downstream. There was a significant increase in dehydrogenase downstream, with the enzyme activity attaining a peak at 600 m, also indicating a gradual reduction of toxicity. Biological oxygen demand (19.56 mg L(-1)) dissolved oxygen (3.97 mg L(-1)) and high lethal dose value (85%) of D. magna also confirmed an initial stress at the point of discharge and recovery downstream. Optical density of surface water demonstrated an increase in suspended particulates and colour after the discharge point, eventually decreasing beyond 400 m. In conclusion, the study highlighted the importance of understanding the biogeochemistry of river systems impacted by industries discharging effluent into them and the invaluable role of a biosensor-based ecotoxicological approach to address effluent hazards, particularly in relation to river sediments.

PCB congener dynamics in a heavily industrialized river catchment

PCB congener concentrations in the water column of a highly industrialized river catchment, the Aire/Calder, in N.E. England were determined weekly on a routine basis, and 2 hourly through selected high flow (flood) events. Bed, suspended and floodplain sediment PCB congener concentrations were also determined along transects of the rivers investigated. Weekly monitoring revealed that the sum of 11 quantified (Sigma11) PCBs rose in concentration by two orders of magnitude during late summer compared to their winter minimum values. This rise was concurrent with sustained periods of low flow. SigmaPCB concentrations were rapidly diluted during high flow (flood) events. Suspended sediment was, on average, 13 times more contaminated with PCBs than bed sediment, with means of 4.0 and 53.8 ng/g, respectively, while floodplain samples had an intermediate concentration of 29.8 ng/g. Principle components analysis (PCA) of congener profiles showed that all three sediment types were similar, but that congener profiles differed considerably between sediment and whole-water samples. There was no change in the percentage contribution of individual PCB congeners apparent from weekly whole-water monitoring. However, the congener pattern in whole-waters changed systematically during high flow events. PCA showed that whole-water samples collected during high flow events had progressively more sediment characteristics, and then returned to whole-water characteristics on cessation of the event. The PCA evidence, dilution of PCB concentrations during events, and suspended sediments more contaminated than bed sediments, indicate that the major sources of PCBs in this catchment are current inputs from sewage treatment works, rather than remobilization of bed sediments.

Welfare regime and social class variation in poverty and economic vulnerability in Europe: an analysis of EU-SILC

In this paper we address a set of interrelated issues. These comprise increasing concerns about reliance on nationally based income poverty measures in the context of EU enlargement, the relative merits of one-dimensional versus multidimensional approaches to poverty and social exclusion and the continuing relevance of class-based explanations of life chances. When identifying economically vulnerable groups we find that, contrary to the situation with national income poverty measures, levels of vulnerability vary systematically across welfare regimes. The multidimensional profile of the economically vulnerable sharply differentiates them from the remainder of the population. While they are also characterised by distinctively higher levels of multiple deprivation, a substantial majority of the economically vulnerable are not exposed to such deprivation. Unlike the national relative income approach, the focus on economic vulnerability reveals a pattern of class differentiation that is not dominated by the contrast between the self-employed and all others. In contrast to a European-wide relative income approach, it also simultaneously captures the fact that absolute levels of vulnerability are distinctively higher among the lower social classes in the less comprehensive and generous welfare regimes while class relativities are significantly sharper at the other end of the spectrum.

Sequencing and its consequences:Path dependence and the relationships between genetics and medicalization

Both advocacy for and critiques of the Human Genome Project assume a self-sustaining relationship between genetics and. medicalization. However, this assumption ignores the ways in which the meanings of genetic research are conditional on its position in sequences of events. Based, on analyses of three conditions for which at least one putative gene or genetic marker has been identified, this article argues that critical junctures in the institutional stabilization of phenotypes and the mechanisms that sustain such classifications over time configure the practices and meanings of genetic research. Path dependence is critical to understanding the lack of consistent fit between genetics and medlcalization.

Electric currents and lens regeneration in the rat

We studied the process of lens regeneration in the rat following an extracapsular lens extraction preserving the anterior lens capsule and anterior lens epithelium. We assessed clinically the clarity of the newly regenerated lens, evaluated changes in the lens electrical currents following surgery and during the regeneration process and correlated these changes with findings on light microscopy. Protein analysis of the regenerated lens was also undertaken. Experiments were performed in 41 Sprague-Dawley rats, sacrificed at 0, 2, 4 and 8 weeks postoperatively. Our results showed that complete lens regeneration occurred 8 weeks postoperatively only if the anterior epithelium was preserved and the lens capsule was closed surgically. Lens electrical currents, altered following surgery, recovered in parallel with the process of regeneration of the lens. The newly regenerated lens was optically clear and biochemical analysis revealed a pattern of protein expression resembling that observed during lens development. In conclusion, complete lens regeneration occurs in the rat and it is possible that lens electrical signals, together with other cues, may play an important role in this process. © 2009 Elsevier Ltd.

Hyperglycemia and adverse pregnancy outcome (HAPO) study:Associations with neonatal anthropometrics

OBJECTIVE-To examine associations of neonatal adiposity with maternal glucose levels and cord serum C-peptide in a multicenter multinational study, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, thereby assessing the Pederson hypothesis linking maternal glycemia and fetal hyperinsulinemia to neonatal adiposity. RESEARCH DESIGN AND METHODS-Eligible pregnant women underwent a standard 75-g oral glucose tolerance test between 24 and 32 weeks gestation (as close to 28 weeks as possible). Neonatal anthropometrics and cord serum C-peptide were measured. Associations of maternal glucose and cord serum C-peptide with neonatal adiposity (sum of skin folds >90th percentile or percent body fat >90th percentile) were assessed using multiple logistic regression analyses, with adjustment for potential confounders, including maternal age, parity, BMI, mean arterial pressure, height, gestational age at delivery, and the baby's sex. RESULTS-Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, cord serum C-peptide results were available for 19,885 babies and skin fold measurements for 19,389. For measures of neonatal adiposity, there were strong statistically significant gradients across increasing levels of maternal glucose and cord serum C-peptide, which persisted after adjustment for potential confounders. In fully adjusted continuous variable models, odds ratios ranged from 1.35 to 1.44 for the two measures of adiposity for fasting, 1-h, and 2-h plasma glucose higher by 1 SD. CONCLUSIONS-These findings confirm the link between maternal glucose and neonatal adiposity and suggest that the relationship is mediated by fetal insulin production and that the Pedersen hypothesis describes a basic biological relationship influencing fetal growth. © 2009 by the American Diabetes Association.