Effect of kidney donation on bone mineral metabolism.

Kidney donation results in reductions in kidney function and lasting perturbations in phosphate homeostasis, which may lead to adverse cardiovascular sequelae. However, the acute effects of kidney donation on bone mineral parameters including regulators of calcium and phosphate metabolism are unknown. We conducted a prospective observational controlled study to determine the acute effects of kidney donation on mineral metabolism and skeletal health. Biochemical endpoints were determined before and after donation on days 1, 2 and 3, 6 weeks and 12 months in donors and at baseline, 6 weeks and 12 months in controls. Baseline characteristic of donors (n = 34) and controls (n = 34) were similar: age (53±10 vs 50±14 years, p = 0.33), BMI (26.3±2.89 vs 25.9±3.65, p = 0.59), systolic BP (128±13 vs 130±6 mmHg, p = 0.59), diastolic BP (80±9 vs 81±9 mmHg, p = 0.68) and baseline GFR (84.4±20.2 vs 83.6±25.2 ml/min/1.73m2, p = 0.89). eGFR reduced from 84.4±20.2 to 52.3±17.5 ml/min/1.73m2 (p<0.001) by day 1 with incomplete recovery by 12 months (67.7±22.6; p = 0.002). Phosphate increased by day 1 (1.1(0.9-1.2) to 1.3(1.1-1.4) mmol/L, p <0.001) but declined to 0.8(0.8-1.0) mmol/L (p<0.001) before normalizing by 6 weeks. Calcium declined on day 1 (p = 0.003) but recovered at 6 weeks or 12 months. PTH and FGF-23 remained unchanged, but α-Klotho reduced by day 1 (p = 0.001) and remained low at 6 weeks (p = 0.02) and 1 year (p = 0.04). In this study, we conclude that kidney donation results in acute disturbances in mineral metabolism characterised by a reduced phosphate and circulating α-Klotho concentration without acute changes in the phosphaturic hormones FGF23 and PTH

Regulation of platelet derived growth factor signalling by LAR protein tyrosine phosphatase: a quantitative phosphoproteomics study

Intracellular signaling pathways are reliant on protein phosphorylation events that are controlled by a balance of kinase and phosphatase activity. Although kinases have been extensively studied, the role of phosphatases in controlling specific cell signaling pathways has been less so. Leukocyte common antigen-related protein (LAR) is a member of the LAR subfamily of receptor-like protein tyrosine phosphatases (RPTPs). LAR is known to regulate the activity of a number of receptor tyrosine kinases, including platelet-derived growth factor receptor (PDGFR). To gain insight into the signaling pathways regulated by LAR, including those that are PDGF-dependent, we have carried out the first systematic analysis of LAR-regulated signal transduction using SILAC-based quantitative proteomic and phosphoproteomic techniques. We haveanalyzed differential phosphorylation between wild-type mouse embryo fibroblasts (MEFs) and MEFs in which the LAR cytoplasmic phosphatase domains had been deleted (LARΔP), and found a significant change in abundance of phosphorylation on 270 phosphosites from 205 proteins because of the absence of the phosphatase domains of LAR. Further investigation of specific LAR-dependent phosphorylation sites and enriched biological processes reveal that LAR phosphatase activity impacts on a variety of cellular processes, most notably regulation of the actin cytoskeleton. Analysis of putative upstream kinases that may play an intermediary role between LAR and the identified LAR-dependent phosphorylation events has revealed a role for LAR in regulating mTOR and JNK signaling

A mitotic recombination map proximal to the APC locus on chromosome 5q and assessment of influences on colorectal cancer risk

Mitotic recombination is important for inactivating tumour suppressor genes by copy-neutral loss of heterozygosity (LOH). Although meiotic recombination maps are plentiful, little is known about mitotic recombination. The APC gene (chr5q21) is mutated in most colorectal tumours and its usual mode of LOH is mitotic recombination.

In the dedicated pursuit of dedicated capital: restoring an indigenous investment ethic to British capitalism

Tony Blair’s landslide electoral victory on May 1 (New Labour Day?) presents the party in power with a rare, perhaps even unprecedented, opportunity to revitalise and modernise Britain’s ailing and antiquated manufacturing economy.* If it is to do so, it must remain true to its long-standing (indeed, historic) commitment to restore an indigenous investment ethic to British capitalism. In this paper we argue that this in turn requires that the party reject the very neo-liberal orthodoxies which it offered to the electorate as evidence of its competence, moderation and ‘modernisation’, which is has internalised, and which it apparently now views as circumscribing the parameters of the politically and economically possible

Hyperspectral remote sensing of cyanobacterial pigments as indicators for cell populations and toxins in eutrophic lakes

The growth of mass populations of toxin-producing cyanobacteria is a serious concern for the ecological status of inland waterbodies and for human and animal health. In this study we examined the performance of four semi-analytical algorithms for the retrieval of chlorophyll a (Chl a) and phycocyanin (C-PC) from data acquired by the Compact Airborne Spectrographic Imager-2 (CASI-2) and the Airborne Imaging Spectrometer for Applications (AISA) Eagle sensor. The retrieval accuracies of the semi-analytical models were compared to those returned by optimally calibrated empirical band-ratio algorithms. The best-performing algorithm for the retrieval of Chl a was an empirical band-ratio model based on a quadratic function of the ratio of re!ectance at 710 and 670 nm (R2=0.832; RMSE=29.8%). However, this model only provided a marginally better retrieval than the best semi-analytical algorithm. The best-performing model for the retrieval of C-PC was a semi-analytical nested band-ratio model (R2=0.984; RMSE=3.98 mg m−3). The concentrations of C-PC retrieved using the semi-analytical model were correlated with cyanobacterial cell numbers (R2=0.380) and the particulate and total (particulate plus dissolved) pools of microcystins (R2=0.858 and 0.896 respectively). Importantly, both the empirical and semi-analytical algorithms were able to retrieve the concentration of C-PC at cyanobacterial cell concentrations below current warning thresholds for cyanobacteria in waterbodies. This demonstrates the potential of remote sensing to contribute to early-warning detection and monitoring of cyanobacterial blooms for human health protection at regional and global scales

Abstracts

Abstracts of papers about Giuseppe Verdi and his works, presented at joint meetings of the AIVS and Greater NY Chapter of the American Musicological Society, 1979-81 (Hepokoski, Lawton, Chusid, Hornick, Nádas, Tomlinson, Garrison, Powers), at the 1982 national meeting of the American Musicological Society (Harwood), and at an NEH-sponsored summer seminar at NYU in 1980 (Beams, Cole, Cordell, Davis, Fry, King, Mason, McCauley, Town)

The Security imaginary: Explaining military isomorphism

This article proposes the notion of a security imaginary as a heuristic tool for exploring military isomorphism (the phenomenon that weapons and military strategies begin to look the same across the world) at a time when the US model of defence transformation is being adopted by an increasing number of countries. Built on a critical constructivist foundation, the security-imaginary approach is contrasted with rationalist and neo-institutionalist ways of explaining military diffusion and emulation. Merging cultural and constructivist themes, the article offers a ‘strong cultural’ argument to explain why a country would emulate a foreign military model and how this model is constituted in and comes to constitute a society’s security imaginary.Web of Scienc

H1N1 Antibody Persistence 1 Year After Immunization With an Adjuvanted or Whole-Virion Pandemic Vaccine and Immunogenicity and Reactogenicity of Subsequent Seasonal Influenza Vaccine: A Multicenter Follow-on Study

Background. We investigated antibody persistence in children 1 year after 2 doses of either an AS03B-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV). Methods. Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination. Results. Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03B-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%–100%) vs 32.4% (95% CI, 21.5%–44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%–99.4%) vs 65.9% (95% CI, 55.3%–75.5%) in those 3–12 years old at immunization, respectively (P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03B-adjuvanted vaccine. Conclusions. This study provides serological evidence that 2 doses of AS03B-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain