Bayesian estimates of linkage disequilibrium

[Background] The maximum likelihood estimator of D' – a standard measure of linkage disequilibrium – is biased toward disequilibrium, and the bias is particularly evident in small samples and rare haplotypes. [Results] This paper proposes a Bayesian estimation of D' to address this problem. The reduction of the bias is achieved by using a prior distribution on the pair-wise associations between single nucleotide polymorphisms (SNP)s that increases the likelihood of equilibrium with increasing physical distances between pairs of SNPs. We show how to compute the Bayesian estimate using a stochastic estimation based on MCMC methods, and also propose a numerical approximation to the Bayesian estimates that can be used to estimate patterns of LD in large datasets of SNPs. [Conclusion] Our Bayesian estimator of D' corrects the bias toward disequilibrium that affects the maximum likelihood estimator. A consequence of this feature is a more objective view about the extent of linkage disequilibrium in the human genome, and a more realistic number of tagging SNPs to fully exploit the power of genome wide association studies.Research supported by NIH/NHLBI grant R21 HL080463-01, NIH/NIDDK 1R01DK069646-01A1 and the Spanish research program [projects TIN2004-06204-C03-02 and TIN2005-02516]

Effects of Elevated CO2 and N Addition on Growth and N2 Fixation of a Legume Subshrub (Caragana microphylla Lam.) in Temperate Grassland in China

It is well demonstrated that the responses of plants to elevated atmospheric CO2 concentration are species-specific and dependent on environmental conditions. We investigated the responses of a subshrub legume species, Caragana microphylla Lam., to elevated CO2 and nitrogen (N) addition using open-top chambers in a semiarid temperate grassland in northern China for three years. Measured variables include leaf photosynthetic rate, shoot biomass, root biomass, symbiotic nitrogenase activity, and leaf N content. Symbiotic nitrogenase activity was determined by the C2H2 reduction method. Elevated CO2 enhanced photosynthesis and shoot biomass by 83% and 25%, respectively, and the enhancement of shoot biomass was significant only at a high N concentration. In addition, the photosynthetic capacity of C. microphylla did not show down-regulation under elevated CO2. Elevated CO2 had no significant effect on root biomass, symbiotic nitrogenase activity and leaf N content. Under elevated CO2, N addition stimulated photosynthesis and shoot biomass. By contrast, N addition strongly inhibited symbiotic nitrogenase activity and slightly increased leaf N content of C. microphylla under both CO2 levels, and had no significant effect on root biomass. The effect of elevated CO2 and N addition on C. microphylla did not show interannual variation, except for the effect of N addition on leaf N content. These results indicate that shoot growth of C. microphylla is more sensitive to elevated CO2 than is root growth. The stimulation of shoot growth of C. microphylla under elevated CO2 or N addition is not associated with changes in N2-fixation. Additionally, elevated CO2 and N addition interacted to affect shoot growth of C. microphylla with a stimulatory effect occurring only under combination of these two factors

Feasibility and tolerability of ophthalmic virtual reality as a medical communication tool in children and young people

Purpose Virtual reality (VR) can be useful in explaining diseases and complications that affect children in order to improve medical communications with this vulnerable patient group. So far, children and young people’s responses to high-end medical VR environments have never been assessed. Methods An unprecedented number of 320 children and young people were given the opportunity to interact with a VR application displaying original ophthalmic volume data via a commercially available tethered head-mounted display (HMD). Participants completed three surveys: demographics and experience with VR, usability and perceived utility of this technology and the Simulator Sickness Questionnaire. The second survey also probed participants for suggestions on improvements and whether this system could be useful for increasing engagement in science. Results A total of 206 sets of surveys were received. 165 children and young people (84 female) aged 12–18 years (mean, 15 years) completed surveys that could be used for analysis. 69 participants (47.59%) were VR-naïve, and 76 (52.41%) reported that they had previous VR experience. Results show that VR facilitated understanding of ophthalmological complications and was reasonably tolerated. Lastly, exposure to VR raised children and young people’s awareness and interest in science. Conclusions The VR platform used was successfully utilized and was well accepted in children to display and interact with volume-rendered 3D ophthalmological data. Virtual reality (VR) is suitable as a novel image display platform in ophthalmology to engage children and young people

Cerebrovascular reactivity among native-raised high altitude residents: an fMRI study

Background: The impact of long term residence on high altitude (HA) on human brain has raised concern among researchers in recent years. This study investigated the cerebrovascular reactivity among native-born high altitude (HA) residents as compared to native sea level (SL) residents. The two groups were matched on the ancestral line, ages, gender ratios, and education levels. A visual cue guided maximum inspiration task with brief breath holding was performed by all the subjects while Blood-Oxygenation-Level-Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) data were acquired from them

Aberration-corrected electron microscopy of nanoparticles

The early history of scanning transmission electron microscopy (STEM) is reviewed as a way to frame the technical issues that make aberration correction an essential upgrade for the study of nanoparticles using STEM. The principles of aberration correction are explained, and the use of aberration-corrected microscopy in the study of nanostructures is exemplified in order to remark the features and challenges in the use of this measuring techniqu

Post-supereruption recovery at Toba Caldera

Large calderas, or supervolcanoes, are sites of the most catastrophic and hazardous events on Earth, yet the temporal details of post-supereruption activity, or resurgence, remain largely unknown, limiting our ability to understand how supervolcanoes work and address their hazards. Toba Caldera, Indonesia, caused the greatest volcanic catastrophe of the last 100 kyr, climactically erupting ~74 ka. Since the supereruption, Toba has been in a state of resurgence but its magmatic and uplift history has remained unclear. Here we reveal that new 14 C, zircon U-Th crystallization and (U-Th)/He ages show resurgence commenced at 69.7±4.5 ka and continued until at least ~2.7 ka, progressing westward across the caldera, as reflected by post-caldera effusive lava eruptions and uplifted lake sediment. The major stratovolcano north of Toba, Sinabung, shows strong geochemical kinship with Toba, and zircons from recent eruption products suggest Toba's climactic magma reservoir extends beneath Sinabung and is being tapped during eruptions

Detecting autozygosity through runs of homozygosity: A comparison of three autozygosity detection algorithms

<p>Abstract</p> <p>Background</p> <p>A central aim for studying runs of homozygosity (ROHs) in genome-wide SNP data is to detect the effects of autozygosity (stretches of the two homologous chromosomes within the same individual that are identical by descent) on phenotypes. However, it is unknown which current ROH detection program, and which set of parameters within a given program, is optimal for differentiating ROHs that are truly autozygous from ROHs that are homozygous at the marker level but vary at unmeasured variants between the markers.</p> <p>Method</p> <p>We simulated 120 Mb of sequence data in order to know the true state of autozygosity. We then extracted common variants from this sequence to mimic the properties of SNP platforms and performed ROH analyses using three popular ROH detection programs, PLINK, GERMLINE, and BEAGLE. We varied detection thresholds for each program (e.g., prior probabilities, lengths of ROHs) to understand their effects on detecting known autozygosity.</p> <p>Results</p> <p>Within the optimal thresholds for each program, PLINK outperformed GERMLINE and BEAGLE in detecting autozygosity from distant common ancestors. PLINK's sliding window algorithm worked best when using SNP data pruned for linkage disequilibrium (LD).</p> <p>Conclusion</p> <p>Our results provide both general and specific recommendations for maximizing autozygosity detection in genome-wide SNP data, and should apply equally well to research on whole-genome autozygosity burden or to research on whether specific autozygous regions are predictive using association mapping methods.</p

Plant Responses to Extreme Climatic Events: A Field Test of Resilience Capacity at the Southern Range Edge

The expected and already observed increment in frequency of extreme climatic events may result in severe vegetation shifts. However, stabilizing mechanisms promoting community resilience can buffer the lasting impact of extreme events. The present work analyzes the resilience of a Mediterranean mountain ecosystem after an extreme drought in 2005, examining shoot-growth and needle-length resistance and resilience of dominant tree and shrub species (Pinus sylvestris vs Juniperus communis, and P. nigra vs J. oxycedrus) in two contrasting altitudinal ranges. Recorded high vegetative-resilience values indicate great tolerance to extreme droughts for the dominant species of pine-juniper woodlands. Observed tolerance could act as a stabilizing mechanism in rear range edges, such as the Mediterranean basin, where extreme events are predicted to be more detrimental and recurrent. However, resistance and resilience components vary across species, sites, and ontogenetic states: adult Pinus showed higher growth resistance than did adult Juniperus; saplings displayed higher recovery rates than did conspecific adults; and P. nigra saplings displayed higher resilience than did P. sylvestris saplings where the two species coexist. P. nigra and J. oxycedrus saplings at high and low elevations, respectively, were the most resilient at all the locations studied. Under recurrent extreme droughts, these species-specific differences in resistance and resilience could promote changes in vegetation structure and composition, even in areas with high tolerance to dry conditions.This study was supported by Ministerio de Ciencia e Innovación (Spanish Government) Projects CGL2008-04794 and CGL2011-29910 to R.Z., and by grant FPU-MEC (AP2005-1561) to A. H