Functional analysis of the C-terminal domain of the WbaP protein that mediates initiation of O antigen synthesis in Salmonella enterica

WbaP catalyzes the transfer of galactose-1-phosphate onto undecaprenyl phosphate (Und-P). The enzyme belongs to a large family of bacterial membrane proteins required for initiation of the synthesis of O antigen lipopolysaccharide and polysaccharide capsules. Previous work in our laboratory demonstrated that the last transmembrane helix and C-terminal tail region of WbaP (WbaP(CT)) are sufficient for enzymatic activity. Here, we demonstrate the cytoplasmic location of the WbaP C-terminal tail and show that WbaPCT domain N-terminally fused to thioredoxin (TrxA-WbaP(CT)) exhibits improved protein folding and enhanced transferase activity. Alanine replacement of highly conserved charged or polar amino acids identified seven critical residues for enzyme activity in vivo and in vitro. Four of these residues are located in regions predicted to be a-helical. These regions and their secondary structure predictions are conserved in distinct WbaP family members, suggesting they may contribute to form a conserved catalytic center.

Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly:a randomized comparative trial

Several studies with erythropoiesis-stimulating agents claim that maintenance therapy of renal anaemia may be possible at extended dosing intervals; however, few studies were randomized, results varied, and comparisons between agents were absent. We report results of a multi-national, randomized, prospective trial comparing haemoglobin maintenance with methoxy polyethylene glycol-epoetin beta and darbepoetin alfa administered once monthly.

LRP-1 variation is not associated with risk of Alzheimer's disease

Alzheimer's disease (AD) is characterised by the extensive deposition of amyloid beta (Aß) within the parenchyma and vasculature of the brain. It is hypothesised that a dysfunction in Aß degradation and/or its removal from the brain may result in accumulation as plaques. Low density lipoprotein receptor-related protein-1 (LRP-1) is a multifunctional receptor shown to be involved in cholesterol metabolism but also the removal of Aß from the brain. Its ability to transport Aß from the brain to the periphery has made it an attractive candidate for involvement in Alzheimer's disease (AD). We have assessed the frequencies of 9 tag- SNPs and the commonly studied synonymous SNP within exon 3 (rs1799986) in a multi-centre AD/control cohort and performed haplotype analysis. We found no evidence from a combined total of 412 controls and 1057 AD patients to support the involvement of LRP-1 variation, including the most commonly studied variant in rs1799986 in conferring genetic susceptibility to increased risk of AD.

Interlocking directorates and conflicts of interest: The Rotterdamsche Bankvereeniging, Müller & Co. and the Dutch financial crisis of the 1920s

How can interlocking directorates cause financial instability for universal banks? A detailed history of the Rotterdamsche Bankvereeninging in the 1920s answers this question in a case study. This large commercial bank adopted a new German-style universal banking business model from the early 1910s, sharing directors with the firms it financed as a means of controlling its interests. Then, in 1924, it required assistance from the Dutch state in order to survive a bank run brought on by public concerns over its close ties with Müller & Co., a trading conglomerate that suffered badly in the economic downturn of the early 1920s. Using a new narrative history combined with an interpretive model, this article shows how the interlocking directorates between the bank and this major client, and in particular the direction of influence of these interlocks, resulted in a conflict of interest that could not be easily overcome.

Rapid changes in the level of Kluane Lake in Yukon Territory over the last millennium

The level of Kluane Lake, the largest lake in Yukon Territory, was lower than at present during most of the Holocene. The lake rose rapidly in the late seventeenth century to a level 12 m above present, drowning forest and stranding driftwood on a conspicuous high-stand beach, remnants of which are preserved at the south end of the lake. Kluane Lake fell back to near its present level by the end of the eighteenth century and has fluctuated within a range of about 3 m over the last 50 yr. The primary control on historic fluctuations in lake level is the discharge of Slims River, the largest source of water to the lake. We use tree ring and radiocarbon ages, stratigraphy and sub-bottom acoustic data to evaluate two explanations for the dramatic changes in the level of Kluane Lake. Our data support the hypothesis of Hugh Bostock, who suggested in 1969 that the maximum Little Ice Age advance of Kaskawulsh Glacier deposited large amounts of sediment in the Slims River valley and established the present course of Slims River into Kluane Lake. Bostock argued that these events caused the lake to rise and eventually overflow to the north. The overflowing waters incised the Duke River fan at the north end of Kluane Lake and lowered the lake to its present level. This study highlights the potentially dramatic impacts of climate change on regional hydrology during the Little Ice Age in glacierised mountains. © 2006 University of Washington.

Comparison of Wavelet Transform and Time-Domain Analysis of Second Trimester Uterine Artery Doppler Waveforms in Screening for Pre-Eclampsia

The aim of this study was to compare time-domain waveform analysis of second-trimester uterine artery Doppler using the resistance index (RI) with waveform analysis using a mathematical tool known as wavelet transform for the prediction of pre-eclampsia (PE). This was a retrospective, nested case-cohort study of 336 women, 37 of whom subsequently developed PE. Uterine artery Doppler waveforms were analysed using both RI and waveform analysis. The utility of these indices in screening for PE was then evaluated using receiver operating characteristic curves. There were significant differences in uterine artery RI between the PE women and those with normal pregnancy outcome. After wavelet analysis, significant difference in the mean amplitude in wavelet frequency band 4 was noted between the 2 groups. The sensitivity for both Doppler RI and frequency band 4 for the detection of PE at a 10% false-positive rate was 45%. This small study demonstrates the application of wavelet transform analysis of uterine artery Doppler waveforms in screening for PE. Further prospective studies are needed in order to clearly define if this analytical approach to waveform analysis may have the potential to improve the detection of PE by uterine artery Doppler screening.

Large-scale spatial patterns in the distribution of Collembola (Hexapoda) species in Antarctic terrestrial ecosystems

We tested whether the distribution of three common springtail species (Gressittacantha terranova, Gomphiocephalus hodgsoni and Friesea grisea) in Victoria Land (Antarctica) could be modelled as a function of latitude, longitude, altitude and distance from the sea.

Victoria Land, Ross Dependency, Antarctica.

Generalized linear models were constructed using species presence/absence data relative to geographical features (latitude, longitude, altitude, distance from sea) across the species' entire ranges. Model results were then integrated with the known phylogeography of each species and hypotheses were generated on the role of climate as a major driver of Antarctic springtail distribution.

Based on model selection using Akaike's information criterion, the species' distributions were: hump-shaped relative to longitude and monotonic with altitude for Gressittacantha terranova; hump-shaped relative to latitude and monotonic with altitude for Gomphiocephalus hodgsoni; and hump-shaped relative to longitude and monotonic with latitude, altitude and distance from the sea for Friesea grisea.

No single distributional pattern was shared by the three species. While distributions were partially a response to climatic spatial clines, the patterns observed strongly suggest that past geological events have influenced the observed distributions. Accordingly, present-day spatial patterns are likely to have arisen from the interaction of historical and environmental drivers. Future studies will need to integrate a range of spatial and temporal scales to further quantify their respective roles.

Evidence for a schizophrenia vulnerability locus on chromosome 8p in the Irish Study of High-Density Schizophrenia Families

This study was an attempt to replicate evidence for a vulnerability locus for schizophrenia and associated disorders in the 8p22-21 region reported by Pulver and colleagues.