Molecular characterization of highly pathogenic H5N1 avian influenza viruses isolated in Sweden in 2006

<p>Abstract</p> <p>Background</p> <p>The analysis of the nonstructural (NS) gene of the highly pathogenic (HP) H5N1 avian influenza viruses (AIV) isolated in Sweden early 2006 indicated the co-circulation of two sub-lineages of these viruses at that time. In order to complete the information on their genetic features and relation to other HP H5N1 AIVs the seven additional genes of twelve Swedish isolates were amplified in full length, sequenced, and characterized.</p> <p>Results</p> <p>The presence of two sub-lineages of HP H5N1 AIVs in Sweden in 2006 was further confirmed by the phylogenetic analysis of approximately the 95% of the genome of twelve isolates that were selected on the base of differences in geographic location, timing and animal species of origin. Ten of the analyzed viruses belonged to sub-clade 2.2.2. and grouped together with German and Danish isolates, while two 2.2.1. sub-clade viruses formed a cluster with isolates of Egyptian, Italian, Slovenian, and Nigerian origin. The revealed amino acid differences between the two sub-groups of Swedish viruses affected the predicted antigenicity of the surface glycoproteins, haemagglutinin and neuraminidase, rather than the nucleoprotein, polymerase basic protein 2, and polymerase acidic protein, the main targets of the cellular immune responses. The distinctive characteristics between members of the two subgroups were identified and described.</p> <p>Conclusion</p> <p>The comprehensive genetic characterization of HP H5N1 AIVs isolated in Sweden during the spring of 2006 is reported. Our data support previous findings on the coincidental spread of multiple sub-lineage H5N1 HPAIVs via migrating aquatic birds to large distance from their origin. The detection of 2.2.1. sub-clade viruses in Sweden adds further data regarding their spread in the North of Europe in 2006. The close genetic relationship of Swedish isolates sub-clade 2.2.2. to the contemporary German and Danish isolates supports the proposition of the introduction and spread of a single variant of 2.2.2. sub-clade H5N1 avian influenza viruses in the Baltic region. The presented findings underline the importance of whole genome analysis.</p

Covariation in population trends and demography reveals targets for conservation action

Wildlife conservation policies directed at common and widespread, but declining, species are difficult to design and implement effectively, as multiple environmental changes are likely to contribute to population declines. Conservation actions ultimately aim to influence demographic rates, but targeting actions towards feasible improvements in these is challenging in widespread species with ranges that encompass a wide range of environmental conditions. Across Europe, sharp declines in the abundance of migratory landbirds have driven international calls for action, but actions that could feasibly contribute to population recovery have yet to be identified. Targeted actions to improve conditions on poor-quality sites could be an effective approach, but only if local conditions consistently influence local demography and hence population trends. Using long-term measures of abundance and demography of breeding birds at survey sites across Europe, we show that co-occurring species with differing migration behaviours have similar directions of local population trends and magnitudes of productivity, but not survival rates. Targeted actions to boost local productivity within Europe, alongside large-scale (non-targeted) environmental protection across non-breeding ranges, could therefore help address the urgent need to halt migrant landbird declines. Such demographic routes to recovery are likely to be increasingly needed to address global wildlife declines.Peer reviewe

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352

Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.Peer reviewe

Wingbeat frequency and the body drag anomaly: wind-tunnel observations on a thrush nightingale (Luscinia Luscinia) and a teal (Anas crecca)

A teal (Anas crecca) and a thrush nightingale (Luscinia luscinia) were trained to fly in the Lund wind tunnel for periods of up to 3 and 16 h respectively. Both birds flew in steady flapping flight, with such regularity that their wingbeat frequencies could be determined by viewing them through a shutter stroboscope. When flying at a constant air speed, the teal\u27s wingbeat frequency varied with the 0.364 power of the body mass and the thrush nightingale\u27s varied with the 0.430 power. Both exponents differed from zero, but neither differed from the predicted value (0.5) at the 1 % level of significance. The teal continued to flap steadily as the tunnel tilt angle was varied from -1&deg; (climb) to +6&deg; (descent), while the wingbeat frequency declined progressively by about 11%. In both birds, the plot of wingbeat frequency against air speed in level flight was U-shaped, with small but statistically significant curvature. We identified the minima of these curves with the minimum power speed (Vmp) and found that the values predicted for Vmp, using previously published default values for the required variables, were only about two-thirds of the observed minimum-frequency speeds. The discrepancy could be resolved if the body drag coefficients (CDb) of both birds were near 0.08, rather than near 0.40 as previously assumed. The previously published high values for body drag coefficients were derived from wind-tunnel measurements on frozen bird bodies, from which the wings had been removed, and had long been regarded as anomalous, as values below 0.01 are given in the engineering literature for streamlined bodies. We suggest that birds of any size that have well-streamlined bodies can achieve minimum body drag coefficients of around 0.05 if the feet can be fully retracted under the flank feathers. In such birds, field observations of flight speeds may need to be reinterpreted in the light of higher estimates of Vmp. Estimates of the effective lift:drag ratio and range can also be revised upwards. Birds that have large feet or trailing legs may have higher body drag coefficients. The original estimates of around CDb=0.4 could be correct for species, such as pelicans and large herons, that also have prominent heads. We see no evidence for any progressive reduction of body drag coefficient in the Reynolds number range covered by our experiments, that is 21600-215 000 on the basis of body cross-sectional diameter

Long flights do not influence immune responses of a long-distance migrant bird: a wind-tunnel experiment

Heavy physical work can result in physiological stress and suppressed immune function. Accordingly, long-distance migrant birds that fly for thousands of km within days can be expected to show immunosuppression, and hence be more vulnerable to infections en route. The red knot Calidris canutus Linnaeus is a long-distance migrant shorebird. We flew red knots the equivalent of 1500 km over 6 days in a wind tunnel. The humoral and cell-mediated immune responses of the flyers were compared to those of non-flying controls. Humoral immunity was measured as antibody production against injected diphtheria and tetanus antigens, and cell-mediated response as phytohemagglutinin-induced wing-web swelling. Blood corticosterone levels, which may modulate immune function, were measured in parallel. The long flights had no detectable effects on humoral or cell-mediated immune responses, or on corticosterone levels. Thus, flight performance per se may not be particularly stressful or immunosuppressive in red knots. Some birds assigned as flyers refused to fly for extended periods. Before flights started, these non-flyers had significantly lower antibody responses against tetanus than the birds that carried out the full flight program. This suggests that only birds in good physical condition may be willing to take on heavy exercise. We conclude that these long-distance migrants appear well adapted to the work load induced by long flights, enabling them to cope with long flight distances without increased stress levels and suppression of immunity. Whether this also applies in the wild, where the migrating birds may face adverse weather and food conditions, remains to be investigated.

Are birds stressed during long-term flights? A wind-tunnel study on circulating corticosterone in the red knot

During endurance flight most birds do not feed and have to rely on their body reserves. Fat and protein is catabolised to meet the high energetic demands. Even though the hormonal regulation of migration is complex and not yet fully understood, the adrenocortical hormone corticosterone crystallizes to play a major role in controlling physiological traits in migratory birds during flight. However, results from field studies are partially equivocal, not least because data from birds during endurance flight are hard to get and present mostly a momentary shot. A wind-tunnel experiment offered the possibility to measure repeatedly under controlled conditions the effect of long flights on the stress hormone corticosterone. In a long-distance migrating shorebird, the red knot Calidris canutus, we measured plasma concentrations of corticosterone within 3 min and after a restraint time of 30 min directly after 2 h and 10 h non-stop flights, respectively, and during rest. Baseline corticosterone levels were unchanged directly after the flights, indicating that endurance flight did not affect corticosterone levels. The adrenocortical response to restraint showed the typical rise in birds during rest, while birds after a 2 or 10 h flight substantially decreased plasma corticosterone concentrations. We suggest that the negative adrenocortical response to restraint after flight is part of the mechanism to reduce the proteolytic effect of corticosterone to save muscle protein and to avoid muscle damaging effects.

Regularization Tools for Training Large-Scale Neural Networks

We present regularization tools for training small-and-medium as well as large-scale artificial feedforward neural networks. The determination of the weights leads to very ill-conditioned nonlinear least squares problems and regularization is often suggested to get control over the network complexity, small variance error, and nice optimization problems. The algorithms proposed solve explicitly a sequence of Tikhonov regularized nonlinear least squares problems. For small-and-medium size problems the Gauss-Newton method is applied to the regularized problem that is much more well-conditioned than the original problem, and exhibits far better convergence properties than a Levenberg-Marquardt method. Numerical results presented also confirm that the proposed implementations are more reliable and efficient than the Levenberg-Marquardt method. For large-scale problems, methods using new special purpose automatic differentiation combined with conjugate gradient methods are proposed. The alg..

MINIMat data

Dataset that contains height for age scores for children participating in the MINIMat trial from birth to ten years of age, the final sample. N = 1054. This dataset supports a paper titled, "Stunted at 10 Years. Linear Growth Trajectories and Stunting from Birth to Pre-Adolescence in a Rural Bangladeshi Cohort"