High dispersal potential has maintained long-term population stability in the North Atlantic copepod Calanus finmarchicus

The cool-water copepod Calanus finmarchicus is a key species in North Atlantic marine ecosystems since it represents an important food resource for the developmental stages of several fish of major economic value. Over the last 40 years, however, data from the Continuous Plankton Recorder survey have highlighted a 70 per cent reduction in C. finmarchicus biomass, coupled with a gradual northward shift in the species's distribution, which have both been linked with climate change. To determine the potential for C. finmarchicus to track changes in habitat availability and maintain stable effective population sizes, we have assessed levels of gene flow and dispersal in current populations, as well as using a coalescent approach together with palaeodistribution modelling to elucidate the historical population demography of the species over previous changes in Earth's climate. Our findings indicate high levels of dispersal and a constant effective population size over the period 359 000-566 000 BP and suggest that C. finmarchicus possesses the capacity to track changes in available habitat, a feature that may be of crucial importance to the species's ability to cope with the current period of global climate change.

DNA methylation profiling in cell models of diabetic nephropathy

We have previously identified differentially expressed genes in cell models of diabetic nephropathy and renal biopsies. Here we have performed quantitative DNA methylation profiling in cell models of diabetic nephropathy. Over 3,000 CpG units in the promoter regions of 192 candidate genes were assessed in unstimulated human mesangial cells (HMCs) and proximal tubular epithelial cells (PTCs) compared to HMCs or PTCs exposed to appropriate stimuli. A total of 301 CpG units across 38 genes (similar to 20%) were identified as differentially methylated in unstimulated HMCs versus PTCs. Analysis of amplicon methylation values in unstimulated versus stimulated cell models failed to demonstrate a >20% difference between amplicons. In conclusion, our results demonstrate that specific DNA methylation signatures are present in HMCs and PTCs, and standard protocols for exposure of renal cells to stimuli that alter gene expression may be insufficient to replicate possible alterations in DNA methylation profiles in diabetic nephropathy.

Fabricating Economic Development

Much of the literature, regardless of academic discipline, presents the publication of Economic Development in 1958 as analogous to a"big bang" event in the creation of modern Ireland. However, such a "big bang" perspective misrepresents the sophistication of economic debates prior to Whitaker's report as well as distorting the interpretation of subsequent developments. This paper reappraises Irish economic thinking before and after the publication of Economic Development. It is argued that an economically "liberal" approach to Keynesianism, such as that favoured by T. K. Whitaker and George O'Brien, lost out in the 1960s to a more interventionist approach: only later did a more liberal approach to macroeconomic policy triumph. The rival approaches to academic economics were in turn linked to wider debates on the influence of religious authorities on Irish higher education. Academic economists were particularly concerned with preserving their intellectual independence and how a shift to planning would keep decisions on resource allocation out of the reach of conservative political and religious leaders.

Exudative AMD subtypes and eligibility for treatment with ranibizumab

Purpose To ascertain the proportion of patients with neovascular age-related macular degeneration (AMD) eligible for intravitreal treatment with monoclonal antibodies to vascular endothelial growth factor, on the basis of inclusion criteria used in pivotal clinical trials.

Association of VEGF-1499C -> T polymorphism with diabetic nephropathy in type 1 diabetes mellitus

Vascular endothelial growth factor (VEGF) is reported to be implicated in the development of diabetic nephropathy. We performed a case-control study to determine if VEGF-2578C -> A, VEGF-1499C -> T, and VEGF-635G -> C single-nucleotide polymorphisms (SNPs) in the VEGF gene are associated with predisposition to diabetic nephropathy in type I diabetes. Genomic DNA was obtained from Irish type I diabetic individuals with nephropathy (cases, n=242) and those without nephropathy (controls, n=301), in addition to 400 healthy control samples. These samples were genotyped for the three SNPs using TaqMan or Pyrosequencing technology. Chi-squared analyses revealed no significant differences in genotype or allele frequencies in cases versus controls for VEGF-2578C -> A (genotype, P=.58; allele, P=.52) and VEGF-635G -> C (genotype, P=.58; allele, P=.33). However, a positive association with diabetic nephropathy was observed for the VEGF-1499T allele in the Northern Ireland population (P

Targets of genome copy number reduction in primary breast cancers identified by integrative genomics

The identification of specific oncogenes and tumor suppressor genes in regions of recurrent aneuploidy is a major challenge of molecular cancer research. Using both oligonucleotide single-nucleotide polymorphism and mRNA expression arrays, we integrated genomic and transcriptional information to identify and prioritize candidate cancer genes in regions of increased and decreased chromosomal copy number in a cohort of primary breast cancers. Confirming the validity of this approach, several regions of previously-known copy number (CN) alterations in breast cancer could be successfully reidentified. Focusing on regions of decreased CN, we defined a prioritized list of eighteen candidate genes, which included ARPIN, FBNI, and LZTSI, previously shown to be associated with cancers in breast or other tissue types, and novel genes such as P29, MORF4LI, and TBCID5. One such gene, the RUNX3 transcription factor, was selected for further study. We show that RUNX3 is present at reduced CNs in proportion to the rest of the tumor genome and that RUNX3 CN reductions can also be observed in a breast cancer series from a different center. Using tissue microarrays, we demonstrate in an independent cohort of over 120 breast tissues that RUNX3 protein is expressed in normal breast epithelium but not fat and stromal tissue, and widely down-regulated in the majority of breast cancers (> 85%). In vitro, RUNX3 overexpression suppressed the invasive potential of MDA-MB-231 breast cancer cells in a matrigel assay. Our results demonstrate the utility of integrative genomic approaches to identify novel potential cancer-related genes in primary tumors. This article contains Supplementary Material available at http:// www.interscience.wiley.com/jpages/1045-2257/suppmat. (c) 2006 Wiley-Liss, Inc.

Detecting Ca2+ sparks on stationary and varying baselines.

Studies concerning the physiological significance of Ca2+ sparks often depend on the detection and measurement of large populations of events in noisy microscopy images. Automated detection methods have been developed to quickly and objectively distinguish potential sparks from noise artifacts. However, previously described algorithms are not suited to the reliable detection of sparks in images where the local baseline fluorescence and noise properties can vary significantly, and risk introducing additional bias when applied to such data sets. Here, we describe a new, conceptually straightforward approach to spark detection in linescans that addresses this issue by combining variance stabilization with local baseline subtraction. We also show that in addition to greatly increasing the range of images in which sparks can be automatically detected, the use of a more accurate noise model enables our algorithm to achieve similar detection sensitivities with fewer false positives than previous approaches when applied both to synthetic and experimental data sets. We propose, therefore, that it might be a useful tool for improving the reliability and objectivity of spark analysis in general, and describe how it might be further optimized for specific applications.

A puzzling periodicity in the pulsating DA white dwarf G 117-B15A

We present time-resolved optical spectrophotometry of the pulsating hydrogen atmosphere (DA) white dwarf G 117-B15A. We find three periodicities in the pulsation spectrum (215 s, 272 s, and 304 s) all of which have been found in earlier studies. By comparing the fractional wavelength dependence of the pulsation amplitudes ( chromatic amplitudes) with models, we confirm a previous report that the strongest mode, at 215 s, has l = 1. The chromatic amplitude for the 272 s mode is very puzzling, showing an increase in fractional amplitude with wavelength that cannot be reproduced by the models for any ` at optical wavelengths. Based on archival HST data, we show that while the behaviour of the 215 s mode at ultra-violet wavelengths is as expected from models, the weird behaviour of the 272 s periodicity is not restricted to optical wavelengths in that it fails to show the expected increase in fractional amplitude towards shorter wavelengths. We discuss possible causes for the discrepancies found for the 272 s variation, but find that all are lacking, and conclude that the nature of this periodicity remains unclear.

Diphosphine analogues of proton sponge: X-ray crystal structure of [Pd(eta(3)-allyl)(dppn)]BF4 center dot CH2Cl2 (dppn equals 1,8-bis(diphenylphosphino)naphthalene)

The X-ray crystal structure of [Pd(eta(3)-allyl)(dppn)]BF4 . CH2Cl2 (1) where dppn = 1,8-bis(diphenylphosphino)naphthalene is reported. Comparison of the conformation of the ligand in 1 with that in the free state shows that there is a relief of strain on complexation analogous to the relief of strain observed upon protonation of proton sponge.