Natural selection on EPAS1 (HIF2 alpha) associated with low hemoglobin concentration in Tibetan highlanders

By impairing both function and survival, the severe reduction in oxygen availability associated with high-altitude environments is likely to act as an agent of natural selection. We used genomic and candidate gene approaches to search for evidence of such genetic selection. First, a genome-wide allelic differentiation scan (GWADS) comparing indigenous highlanders of the Tibetan Plateau (3,200 3,500 m) with closely related lowland Han revealed a genome-wide significant divergence across eight SNPs located near EPAS1. This gene encodes the transcription factor HIF2 alpha, which stimulates production of red blood cells and thus increases the concentration of hemoglobin in blood. Second, in a separate cohort of Tibetans residing at 4,200 m, we identified 31 EPAS1 SNPs in high linkage disequilibrium that correlated significantly with hemoglobin concentration. The sex-adjusted hemoglobin concentration was, on average, 0.8 g/dL lower in the major allele homozygotes compared with the heterozygotes. These findings were replicated in a third cohort of Tibetans residing at 4,300 m. The alleles associating with lower hemoglobin concentrations were correlated with the signal from the GWADS study and were observed at greatly elevated frequencies in the Tibetan cohorts compared with the Han. High hemoglobin concentrations are a cardinal feature of chronic mountain sickness offering one plausible mechanism for selection. Alternatively, as EPAS1 is pleiotropic in its effects, selection may have operated on some other aspect of the phenotype. Whichever of these explanations is correct, the evidence for genetic selection at the EPAS1 locus from the GWADS study is supported by the replicated studies associating function with the allelic variants.

Control dynamics of severe acute respiratory syndrome transmission

Severe acute respiratory syndrome (SARS) is a serious disease with many puzzling features. We present a simple, dynamic model to assess the epidemic potential of SARS and the effectiveness of control measures. With this model, we analysed the SARS epidemic data in Beijing. The data fitting gives the basic case reproduction number of 2.16 leading to the outbreak, and the variation of the effective reproduction number reflecting the control effect. Noticeably, our study shows that the response time and the strength of control measures have significant effects on the scale of the outbreak and the lasting time of the epidemic.

Air flow over a mountain and the convective boundary-layer

In this paper, the analytical model coupling the convective boundary layer (CBL) with the free atmosphere developed by Qi and Fu (1992) is improved. And by this improved model, the interaction between airflow over a mountain and the CBL is further discussed. The conclusions demonstrate: (1) The perturbation potential temperatures in the free atmosphere can counteract the effect of orographic thermal forcing through entraining and mixing in the CBL. If u(M)BAR > u(F)BAR, the feedback of the perturbation potential temperatures in the free atmosphere is more important than orographic thermal forcing, which promotes the effect of interfacial waves. If u(M)BAR < u(F)BAR, orographic thermal forcing is more important, which makes the interfacial height and the topographic height identical in phase, and the horizontal speeds are a maximum at the top of the mountain. (2) The internal gravity waves propagating vertically in the free atmosphere cause a strong downslope wind to become established above the lee slope in the CBL and result in the hydraulic jump at the top of the CBL. (3) With the CBL deepening, the interfacial gravity waves induced by the potential temperature jump at the top of the CBL cause the airflow in the CBL to be subcritical.

Soluble Angiopoietin Receptor Tie-2 In Patients With Acute Myocardial Infarction And Its Detection By Optical Protein-Chip

The Tie-2 receptor has been shown to play a role in angiogenesis in atherosclerosis. The conventional method assaying the level of soluble Tie-2 (sTie-2) was ELISA. However, this method has some disadvantages. The aims of this research are to establish a more simple detection method, the optical protein-chip based on imaging ellipsomtry (OPC-IE) applying to Tie-2 assay. The sTie-2 biosensor surface on silicon wafer was prepared first, and then serum levels of sTie-2 in 38 patients with AMI were measured on admission (day 1), day 2, day 3 and day 7 after onset of chest pain and 41 healthy controls by ELISA and OPC-IE in parallel. Median level of sTie-2 increased significantly in the AMI patients when compared with the controls. Statistics showed there was a significant correlation in sTie-2 results between the two methods (r=0.923, P0.01). The result of this study showed that the level of sTie-2 increased in AMI, and OPC-IE assay was a fast, reliable, and convenient technique to measure sTie-2 in serum.