ABSTRACT
As the main carrier of oxygen delivery in the blood circulation system, hemoglobin (Hb) plays a key role in the adaptation of animals to high altitude hypoxia.In this paper, we combined analysis of genome, transcriptome, molecular evolution, homology modeling and molecular dynamics simulation, and explored the molecular mechanisms of increased blood oxygen affinity of Pseudopodoces humilis.Our results showed that the prenatal expressed p gene was highly expressed in the adult Pseudopodoces humilis (RPKM = 32.22) compared to Parus major (RPKM = 0), and this may result in the presence of two additional p-type Hbs with high oxygen affinity in the blood of P.humilis, i.e.(al>p)2 and (aAp)2.The PA25G-A and pA55L-I mutations may increase the van der Waals force between the B and D helices, which might eventually make the entire Pv subunit more compact and finally reduce the number of hydrogen bonds between a dimers, hence the transition from T state to R state is prone to occur.The two mutations of (3a43A-S and pA44S-N could change the conformation and polarity of the heme pocket opening, thus making the solution easier to flow into/out of the heme pocket and therefore facilitating the gas exchange.The pA90E-K mutation in P.humilis has undergone strong positive selection, which could increase the basicity of pA-type Hb, thereby offsetting the decrease in Hb-02 affinity caused by the Bohr effect.In addition, we also found that aA44P-S and pA43A-S mutations may increase the hydrophilicity of otA and pv type Hbs, which is beneficial to the accumulation of Hb to a higher concentration in red blood cells.Collectively, the prenatal Hb genes highly expressed in the adult together with the genetic based changes in intrinsic 0, affinity and physicochemical property of aA and pA Hb could be the main causes for the increase in blood oxygen affinity of P.humilus.
ABSTRACT
<p><b>OBJECTIVE</b>Calibrated Automated Thrombogram(CAT) is a test to monitor the generation of thrombin. It can be described by four parameters: lag time, peak thrombin, endogenous thrombin potential (ETP) and time to peak (ttPeak). This study aims to determine the normal ranges of CAT parameters in Chinese, and evaluate whether thrombin generation is correlated with the concentration of heparin/low molecular weight heparin.</p><p><b>METHODS</b>Plasma from 120 healthy subjects were collected to determine the normal rangea of CAT parameters in Chinese. Normal plasma pool (NPP, n=25) spiked with different concentrations of heparin or enoxaparin were used to detecte CAT parameters. The overall and age specific normal ranges of CAT parameters were calculated using descriptive statistics method with mean±2SD. The correlation between CAT parameters and age or concentrations of heparin, enoxaparin were analyzed with linear regression model.</p><p><b>RESULTS</b>The normal ranges for lag time, peak thrombin, ETP, ttPeak in the subjects were 3.648±2.465 min, 367.39±151.93 nmol/L, 2277±1030 nmol/L•min and 6.372±4.280 min respectively. Age was linearly correlated with lag time (r=-0.6583, P<0.0001), peak thrombin (r=0.4863, P<0.0001), ETP (r=0.3608, P<0.0014) and ttPeak (r=-0.6313, P<0.0001). The values of ETP/peak ratio were linearly correlated with concentrations of heparin.</p><p><b>CONCLUSION</b>The normal ranges of four CAT parameters for Chinese were determined. CAT parameters are associated with age. ETP/peak ratio could be used to monitor the process of anticoagulation therapy.</p>