[Co-accumulation characters of soil organic carbon and nitrogen under broadleaved Korean pine and Betula platyphylla secondary forests in Changbai Mountain, China.] / 长白山阔叶红松林和杨桦次生林土壤有机碳氮的协同积累特征.

The retrogressive succession is an important driver for dynamics of soil organic carbon (SOC) and total nitrogen (TN). We studied the quantitative distribution and synergistic accumulation characteristics of soil organic carbon and nitrogen in the primary broadleaved Korean pine (KP) forest and Betula platyphylla (BP) secondary forest in Changbai Mountain through paired plot approach. Further, we analyzed the changes of carbon pool and carbon sink effect in temperate forest soil caused by secondary succession and their carbon-nitrogen coupling mechanism. The results showed that the BP forest accumulated more organic carbon and nitrogen in the surface and subsurface soil (0-20 cm) than the KP forest, with relatively low soil C/N. Compared with KP forest, soil organic carbon storage in BP forest (0-20 cm) was higher by 14.7 t·hm-2, equivalent to a soil carbon sink gain of 29.4 g·m-2·a-1. SOC and TN concentrations were positively correlated in each soil layer of all forest types, causing a co-accumulative relationship between SOC and TN. The coefficient of determination (R2) between SOC and TN in the upper soil layers of BP forest was significantly higher than that of the KP forest, indicating that SOC accumulation under the relatively N-rich BP forest was more dependent on the accumulation of organic nitrogen. In the upper soil layers (0-10 cm) where organic matter concentrated, there was no significant difference in light fraction organic carbon and nitrogen stock between the two forest types, whereas the content, stock, and allocation percentage of heavy fraction organic carbon and nitrogen of BP forest were all significantly higher than that of the KP forest, with an average increment of 8.5 t·hm-2 in heavy fraction organic carbon stock. Those results indicated that the increase of soil organic carbon and nitrogen during secondary succession was mainly due to the increases of soil organic carbon and nitrogen pools in mineral-bound stability. The carbon-nitrogen coupling mechanisms in litter decomposition and soil organic matter formation was an important driving mechanisms underlying the changes of soil organic carbon and nitrogen pools during secondary succession.

Clinical trial data management and quality metrics system / 药学学报

Data quality management system is essential to ensure accurate, complete, consistent, and reliable data collection in clinical research. This paper is devoted to various choices of data quality metrics. They are categorized by study status, e.g. study start up, conduct, and close-out. In each category, metrics for different purposes are listed according to ALCOA+ principles such us completeness, accuracy, timeliness, traceability, etc. Some general quality metrics frequently used are also introduced. This paper contains detail information as much as possible to each metric by providing definition, purpose, evaluation, referenced benchmark, and recommended targets in favor of real practice. It is important that sponsors and data management service providers establish a robust integrated clinical trial data quality management system to ensure sustainable high quality of clinical trial deliverables. It will also support enterprise level of data evaluation and bench marking the quality of data across projects, sponsors, data management service providers by using objective metrics from the real clinical trials. We hope this will be a significant input to accelerate the improvement of clinical trial data quality in the industry.

Inhibitory effects of purified antibody against α-1 repeat (117-137) on Na(+)-Ca(2+) exchange and L-type Ca(2+) currents in rat cardiomyocytes.

Considering that α-1 repeat region may be involved in the ion binding and translocation of Na(+)-Ca(2+) exchanger (NCX), it is possible that the antibodies against NCX α-1 repeat may have a crucial action on NCX activity. The aim of the present study is to investigate the effect of antibody against α-1 repeat (117-137), designated as α-1(117-137), on NCX activity. The antibody against the synthesized α-1(117-137) was prepared and affinity-purified. Whole-cell patch clamp technique was used to study the change of Na(+)-Ca(2+) exchange current (I(Na/Ca)) in adult rat cardiomyocytes. To evaluate the functional specificity of this antibody, its effects on L-type Ca(2+) current (I(Ca,L)), voltage-gated Na(+) current (I(Na)) and delayed rectifier K(+) current (I(K)) were also observed. The amino acid sequences of α-1(117-137) in NCX and residues 1 076-1 096 within L-type Ca(2+) channel were compared using EMBOSS Pairwise Alignment Algorithms. The results showed that outward and inward I(Na/Ca) were decreased by the antibody against α-1(117-137) dose-dependently in the concentration range from 10 to 160 nmol/L, with IC(50) values of 18.9 nmol/L and 22.4 nmol/L, respectively. Meanwhile, the antibody also decreased I(Ca,L) in a concentration-dependent manner with IC(50) of 22.7 nmol/L. No obvious effects of the antibody on I(Na) and I(K) were observed. Moreover, comparison of the amino acid sequences showed there was 23.8% sequence similarity between NCX α-1(117-137) and residues 1 076-1 096 within L-type Ca(2+) channel. These results suggest that antibody against α-1(117-137) is a blocking antibody to NCX and can also decrease I(Ca,L) in a concentration-dependent manner, while it does not have obvious effects on I(Na) and I(K).

Stimulation of Na+-Ca2+ exchange by purified antibody against alpha-2 repeat of Na+-Ca2+ exchanger in rat cardiomyocytes.

AIM: The aim of the present study was to investigate the effect of the antibody against alpha-2 repeat on Na+-Ca2+ exchanger (NCX) current (I(Na/Ca)). To evaluate the functional specificity of this antibody, its effects on L-type Ca2+ current (I(Ca,L)), voltage-gated Na+ current (I(Na)) and delayed rectifier K+ current (I(K)) were also observed. METHODS: The whole-cell patch-clamp technique was used in this study. RESULTS: The antibody against alpha-2 repeat augmented both the outward and inward Na+-Ca2+ exchanger current concentration-dependently, with EC(50) values of 27.9 nmol/L and 24.7 nmol/L, respectively. Meanwhile, the antibody could also increase I(Ca,L) in a concentration-dependent manner with the EC(50) of 33.6 nmol/L. Effects of the antibody on I(Na) and I(K) were not observed in the present study. CONCLUSION: The present results suggest that antibody against alpha-2 repeat is a stimulating antibody to NCX and could also increase I(Ca,L) in a concentration-dependent manner, but did not have an obvious effect on I(Na) and I(K).

[Effects of neuropeptide Y on ion channels in ventricular myocytes].

Neuropeptide Y (NPY) co-exists with norepinephrine (NE) in sympathetic terminals, and is the most abundant neuropeptide in myocardium. Many studies have focused on the effects of NE on ion channels in cardiac myocytes and its physiological significance has been elucidated relatively profoundly. There have been few investigations, however, on the physiological significance of NPY in myocardium. The effects of NPY on L-type Ca2+ channel currents (I(Ca-L)) were evaluated in some studies and different results were presented, which might be attributed to the different species of animal tested and different methods used. It is necessary, therefore, to study the effects of NPY on ion channels in cardiac myocytes systematically and further to discuss the biological significance of their coexistence with NE in sympathetic terminals. The single ventricular myocytes from adult rat or guinea pig (only for measuring I(K)) were prepared using enzymatic dispersion. I(Ca-L), I(to), I(Na/Ca), I(Na) and I(K) in the cellular membrane were observed using whole cell voltage-clamp recording. In the present study, NPY from 1.0 to 100 nmol/L dose-dependently inhibited I(Ca-L) (P<0.01, n=5). The maximal rate of inhibition in this study reached 39% and IC(50) was 1.86 nmol/L. NPY had no effect on the voltage-dependence of calcium current amplitude and on the voltage-dependence of the steady-state gating variables. I(Ca-L) was activated at -30 mV, reaching the maximum at 0 mV. When both NE and NPY were applied with a concentration ratio of 500:1, 10 nmol/L NPY inhibited I(Ca-L) that had been increased by 5 mumol/L NE, which was consistent with the effect of NPY only on I(Ca-L). NPY also inhibited I(Na/Ca). At a concentration of 10 nmol/L, NPY inhibited inward and outward I(Na/Ca) from (0.27+/-0.11) pA/pF and (0.45+/-0.12) pA/pF to (0.06+/-0.01) pA/pF and (0.27+/-0.09) pA/pF, respectively (P<0.05, n=4). NPY at 10 nmol/L increased I(to) from (12.5+/-0.70) pA/pF to (14.7+/-0.59) pA/pF(P<0.05, n=4). NPY at 10 nmol/L did not affect I(Na) in rat myocytes and I(K) in guinea pig myocytes. NPY increased the speed of action potential depolarization and reduced action potential duration of I(Ca-L), I(Na/Ca) and I(to), which contributed to the reduction of contraction. These results indicate that the effects of NPY are opposite to the effects of NE on ion channels of cardiac myocytes.

Enhancement of sodium-calcium exchange induces positive inotropic action and potentiates ouabain effect in rat hearts.

To study the inotropic effect of enhanced Na(+)-Ca(2+) exchange in the rat papillary muscles and isolated heart, the developed tension in the rat papillary muscles was measured and the left ventricular functions were assessed in the isolated rat heart. E-4031, a selective activator for Na(+)-Ca(2+) exchange in rats, concentration-dependently increased the developed contractile tension in the rat papillary muscles (P<0.05, n=6) and the left ventricular functions in the isolated heart; KB-R7943, a selective Na(+)-Ca(2+) exchange inhibitor, exhibited opposite effect. A combination of 0.5 micromol/L ouabain and 3.0 micromol/L E-4031 resulted in a potentiation of the developed contractile tension of the rat papillary muscles from 0.25+/-0.03 g to 0.29+/-0.04 g. The combination also enhanced the augmentation of the left ventricular functions induced by ouabain. These results indicate that E-4031 exerts a positive inotropic effect on the rat papillary muscles and isolated heart via increasing the activity of Na(+)-Ca(2+) exchange, and potentiates the positive inotropic effects of ouabain.

Inotropic effects of MCI-154 on rat cardiac myocytes.

Calcium sensitizers exert positive inotropic effects without increasing intracellular Ca(2+). Thus, they avoid the undesired effects of Ca(2+) overload such as arrhythmias and cell injury, but most of them may impair myocyte relaxation. However, MCI-154, also a calcium sensitizer, has no impairment to cardiomyocyte relaxation. To clarify the underlying mechanisms, we examined the effects of MCI-154 on Ca(2+) transient and cell contraction using ion imaging system, and its influence on L-type Ca(2+) current and Na(+)/ Ca(2+) exchange current with patch clamp technique in rat ventricular myocytes as well. The results showed that: (1) MCI-154 (1-100 micromol/L) had no effect on L-type Ca(2+) current; (2) MCI-154 concentration-dependently increased cell shortening from 5.00+/-1.6 microm of control to 6.2+/-1.6 microm at 1 micromol/L, 8.7+/-1.6 microm at 10 micromol/L and 14.0+/-1.4 microm at 100 micromol/L, respectively, with a slight increase in Ca(2+) transient amplitude and an abbreviation of Ca(2+) transient restore kinetics assessed by time to 50% restore (TR(50)) and time to 90% restore (TR(90)); (3) MCI-154 dose-dependently increased the electrogenic Na(+)/ Ca(2+) exchange current both in the inward and the outward directions in rat ventricular myocytes. These results indicate that MCI-154 exerted a positive inotropic action without impairing myocyte relaxation. The stimulation of inward Na(+)/ Ca(2+) exchange current may accelerate the Ca(2+) efflux, leading to abbreviations of TR(50) and TR(90) in rat myocytes. The findings suggest that the improvement by MCI-154 of myocyte relaxation is attributed to the forward mode of Na(+)/ Ca(2+) exchange.