The D153del mutation in GNB3 gene causes tissue specific signalling patterns and an abnormal renal morphology in rge chickens

Background The GNB3 gene is expressed in cone but not rod photoreceptors of vertebrates, where it acts as the β transducin subunit in the colour visual transduction process. A naturally occurring mutation ‘D153del’ in the GNB3 gene causes the recessively inherited blinding phenotype retinopathy globe enlarged (rge) disease in chickens. GNB3 is however also expressed in most other vertebrate tissues suggesting that the D153del mutation may exert pathological effects that outlie from eye. Principal Findings Recombinant studies in COS-7 cells that were transfected with normal and mutant recombinant GNB3 constructs and subjected to cycloheximide chase showed that the mutant GNB3d protein had a much shorter half life compared to normal GNB3. GNB3 codes for the Gβ3 protein subunit that, together with different Gγ and Gα subunits, activates and regulates phosphorylation cascades in different tissues. As expected, the relative levels of cGMP and cAMP secondary messengers and their activated kinases such as MAPK, AKT and GRK2 were also found to be altered significantly in a tissue specific manner in rge chickens. Histochemical analysis on kidney tissue sections, from rge homozygous affected chickens, showed the chickens had enlargement of the glomerular capsule, causing glomerulomegaly and tubulointerstitial inflammation whereas other tissues (brain, heart, liver, pancreas) were unaffected. Significance These findings confirm that the D153del mutation in GNB3 gene targets GNB3 protein to early degradation. Lack of GNB3 signalling causes reduced phosphorylation activity of ERK2 and AKT leading to severe pathological phenotypes such as blindness and renal abnormalities in rge chickens

Climatic and Biogeochemical Effects of a Galactic Gamma-Ray Burst

It is likely that one or more gamma-ray bursts within our galaxy have strongly irradiated the Earth in the last Gy. This produces significant atmospheric ionization and dissociation, resulting in ozone depletion and DNA-damaging ultraviolet solar flux reaching the surface for up to a decade. Here we show the first detailed computation of two other significant effects. Visible opacity of NO2 is sufficient to reduce solar energy at the surface up to a few percent, with the greatest effect at the poles, which may be sufficient to initiate glaciation. Rainout of dilute nitric acid is could have been important for a burst nearer than our conservative nearest burst. These results support the hypothesis that the characteristics of the late Ordovician mass extinction are consistent with GRB initiation.Comment: 12 pages, 2 figures, in press at Geophysical Research Letters. Minor revisions, including details on falsifying the hypothesi

Fatal Cases of Influenza A in Childhood

In the northern hemisphere winter of 2003–04 antigenic variant strains (A/Fujian/411/02 –like) of influenza A H3N2 emerged. Circulation of these strains in the UK was accompanied by an unusually high number of laboratory confirmed influenza associated fatalities in children. This study was carried out to better understand risk factors associated with fatal cases of influenza in children.Case histories, autopsy reports and death registration certificates for seventeen fatal cases of laboratory confirmed influenza in children were analyzed. None had a recognized pre-existing risk factor for severe influenza and none had been vaccinated. Three cases had evidence of significant bacterial co-infection. Influenza strains recovered from fatal cases were antigenically similar to those circulating in the community. A comparison of protective antibody titres in age stratified cohort sera taken before and after winter 2003–04 showed that young children had the highest attack rate during this season (21% difference, 95% confidence interval from 0.09 to 0.33, p = 0.0009). Clinical incidences of influenza-like illness (ILI) in young age groups were shown to be highest only in the years when novel antigenic drift variants emerged.This work presents a rare insight into fatal influenza H3N2 in healthy children. It confirms that circulating seasonal influenza A H3N2 strains can cause severe disease and death in children in the apparent absence of associated bacterial infection or predisposing risk factors. This adds to the body of evidence demonstrating the burden of severe illness due to seasonal influenza A in childhood

Supersymmetry on a Spatial Lattice

We construct a variety of supersymmetric gauge theories on a spatial lattice, including N=4 supersymmetric Yang-Mills theory in 3+1 dimensions. Exact lattice supersymmetry greatly reduces or eliminates the need for fine tuning to arrive at the desired continuum limit in these examples.Comment: Version 3: Text brought in line with published version (extended discussion of orbifolding

The advantages of the use of discs containing single agents in disc diffusion testing of the susceptibility of Aeromonas salmonicida to potentiated sulphonamides

Peer-reviewed. Released with a Creative Commons Attribution Non-Commercial No Derivatives LicenseThe susceptibilities of 106 strains of Aeromonas salmonicida to trimethoprim/sulfamethoxazole (SFT) were determined in two laboratories using the Clinical and Laboratory Standards Institute's M42-A disc diffusion protocols. The data generated by the use of discs containing 25 μg SFT (SFT25) allowed the strains to be placed into two groups. Strains in one group (17 strains) generated no inhibition zones and the zones obtained from the other 89 strains were distributed over a wide range but showed no natural division into separate sub-classes. A further investigation performed by one of the participating laboratories, of the susceptibility of 91 of these 106 strains used discs containing 100 μg sulfmethoxazole (SFM100) and 5 μg trimethoprim (TMP5). Application of normalised resistance interpretation to these data allowed the estimation of epidemiological cut-off values for WT strains of ≥ 9 mm for SFM100 and ≥ 21 mm for TMP5. This investigation demonstrated the presence of three distinct phenotypic classes, one containing strains manifesting wild type susceptibility to both agents, another containing strains manifesting non-wild type susceptibility to both and a third containing strains manifesting wild type susceptibility with respect to TMP but non-wild type with respect to SFM. Analysis demonstrated the inability of SFT25 discs to generate data that allowed the separate identification of strains that were fully susceptible to both TMP and SFM from those that were fully susceptible to TMP but were not fully susceptible to SFM. It is recommended that, in investigation of the susceptibility to potentiated sulphonamides of isolates from diseased fish, separate discs, containing the individual components of the mixture, should be employed

Global Mortality Estimates for the 2009 Influenza Pandemic from the GLaMOR Project: A Modeling Study

Background: Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substantially higher. We estimated the 2009 pandemic mortality burden through statistical modeling of mortality data from multiple countries. Methods and Findings: We obtained weekly virology and underlying cause-of-death mortality time series for 2005–2009 for 20 countries covering ,35% of the world population. We applied a multivariate linear regression model to estimate pandemic respiratory mortality in each collaborating country. We then used these results plus ten country indicators in a multiple imputation model to project the mortality burden in all world countries. Between 123,000 and 203,000 pandemic respiratory deaths were estimated globally for the last 9 mo of 2009. The majority (62%–85%) were attributed to persons under 65 y of age. We observed a striking regional heterogeneity, with almost 20-fold higher mortality in some countries in the Americas than in Europe. The model attributed 148,000–249,000 respiratory deaths to influenza in an average prepandemic season, with only 19% in persons ,65 y. Limitations include lack of representation of low-income countries among single-country estimates and an inability to study subsequent pandemic waves (2010–2012). Conclusions: We estimate that 2009 global pandemic respiratory mortality was ,10-fold higher than the World Health Organization’s laboratory-confirmed mortality count. Although the pandemic mortality estimate was similar in magnitude to that of seasonal influenza, a marked shift toward mortality among persons ,65 y of age occurred, so that many more life-years were lost. The burden varied greatly among countries, corroborating early reports of far greater pandemic severity in the Americas than in Australia, New Zealand, and Europe. A collaborative network to collect and analyze mortality and hospitalization surveillance data is needed to rapidly establish the severity of future pandemics

Popular attitudes to memory, the body, and social identity : the rise of external commemoration in Britain, Ireland, and New England

A comparative analysis of samples of external memorials from burial grounds in Britain, Ireland and New England reveals a widespread pattern of change in monument style and content, and exponential growth in the number of permanent memorials from the 18th century onwards. Although manifested in regionally distinctive styles on which most academic attention has so far been directed, the expansion reflects global changes in social relationships and concepts of memory and the body. An archaeological perspective reveals the importance of external memorials in articulating these changing attitudes in a world of increasing material consumption