FKBP12.6 protects heart from AngII‐induced hypertrophy through inhibiting Ca2+/calmodulin‐mediated signalling pathways in vivo and in vitro

We previously observed that disruption of FK506‐binding protein 12.6 (FKBP12.6) gene resulted in cardiac hypertrophy in male mice. Studies showed that overexpression of FKBP12.6 attenuated thoracic aortic constriction (TAC)‐induced cardiac hypertrophy in mice, whereas the adenovirus‐mediated overexpression of FKBP12.6 induced hypertrophy and apoptosis in cultured neonatal cardiomyocytes, indicating that the role of FKBP12.6 in cardiac hypertrophy is still controversial. In this study, we aimed to investigate the roles and mechanisms of FKBP12.6 in angiotensin II (AngII)‐induced cardiac hypertrophy using various transgenic mouse models in vivo and in vitro. FKBP12.6 knockout (FKBP12.6^?/?) mice and cardiac‐specific FKBP12.6 overexpressing (FKBP12.6 TG) mice were infused with AngII (1500 ng/kg/min) for 14 days subcutaneously by implantation of an osmotic mini‐pump. The results showed that FKBP12.6 deficiency aggravated AngII‐induced cardiac hypertrophy, while cardiac‐specific overexpression of FKBP12.6 prevented hearts from the hypertrophic response to AngII stimulation in mice. Consistent with the results in vivo, overexpression of FKBP12.6 in H9c2 cells significantly repressed the AngII‐induced cardiomyocyte hypertrophy, seen as reductions in the cell sizes and the expressions of hypertrophic genes. Furthermore, we demonstrated that the protection of FKBP12.6 on AngII‐induced cardiac hypertrophy was involved in reducing the concentration of intracellular Ca²⁺ ([Ca²⁺]i), in which the protein significantly inhibited the key Ca²⁺/calmodulin‐dependent signalling pathways such as calcineurin/cardiac form of nuclear factor of activated T cells 4 (NFATc4), calmodulin kinaseII (CaMKII)/MEF‐2, AKT/Glycogen synthase kinase 3β (GSK3β)/NFATc4 and AKT/mTOR signalling pathways. Our study demonstrated that FKBP12.6 protects heart from AngII‐induced cardiac hypertrophy through inhibiting Ca²⁺/calmodulin‐mediated signalling pathways.     

中国瓜馥木属(番荔枝科)一新记录种

报道了中国番荔枝科瓜馥木属(Annonaceae:Fissistigma)一新记录种——瘤果瓜馥木[F.thorelii(Pierre ex FinetGagnep.)Merr.]。该种在中国产于云南省红河县,凭证标本保存在西双版纳热带植物园标本馆(HITBC)。该种的主要特征是幼枝、花、果均被褐色粗短硬毛,且果实表面布满瘤状突起。     

Bufalin Reverses Resistance to Sorafenib by Inhibiting Akt Activation in Hepatocellular Carcinoma: The Role of Endoplasmic Reticulum Stress

Sorafenib is the standard first-line therapeutic treatment for patients with advanced hepatocellular carcinoma (HCC), but its use is hampered by the development of drug resistance. The activation of Akt by sorafenib is thought to be responsible for this resistance. Bufalin is the major active ingredient of the traditional Chinese medicine Chan su, which inhibits Akt activation; therefore, Chan su is currently used in the clinic to treat cancer. The present study aimed to investigate the ability of bufalin to reverse both inherent and acquired resistance to sorafenib. Bufalin synergized with sorafenib to inhibit tumor cell proliferation and induce apoptosis. This effect was at least partially due to the ability of bufalin to inhibit Akt activation by sorafenib. Moreover, the ability of bufalin to inactivate Akt depended on endoplasmic reticulum (ER) stress mediated by inositol-requiring enzyme 1 (IRE1). Silencing IRE1 with siRNA blocked the bufalin-induced Akt inactivation, but silencing eukaryotic initiation factor 2 (eIF2) or C/EBP-homologous protein (CHOP) did not have the same effect. Additionally, silencing Akt did not influence IRE1, CHOP or phosphorylated eIF2α expression. Two sorafenib-resistant HCC cell lines, which were established from human HCC HepG2 and Huh7 cells, were refractory to sorafenib-induced growth inhibition but were sensitive to bufalin. Thus, Bufalin reversed acquired resistance to sorafenib by downregulating phosphorylated Akt in an ER-stress-dependent manner via the IRE1 pathway. These findings warrant further studies to examine the utility of bufalin alone or in combination with sorafenib as a first- or second-line treatment after sorafenib failure for advanced HCC.     

Temporal and spatial variability of chlorophyll <Emphasis Type="Italic">a</Emphasis> concentration in Lake Taihu using MODIS time-series data

In order to predict the distribution of chlorophyll a synoptically in Lake Taihu from 2006 to 2008, a common empirical algorithm was developed to relate time series chlorophyll a concentrations in the lake to reflectance derived as a function of band 2 MODIS data (r ² = 0.907, n = 145) using time series from 2005. The empirical model was further validated with chlorophyll a data from a 2008 to 2009 dataset, with RMSE < 7.48 μg l⁻¹ and r ² = 0.978. The seasonal and inter-annual variability of the surface chlorophyll a concentration from 2006 to 2008 was then examined using Empirical Orthogonal Function (EOF) analysis. The results revealed that the first four modes were significant, explaining 54.0% of the total chlorophyll a variance, and indicated that during the summer, algal blooms always occur in the northern bays, Meiliang Bay and Gonghu Bay, while they occur along the southwestern lakeshore during early summer, fall, and even early winter. The inter-annual variance analysis showed that the duration of algal blooms was from April to December of 2007, which was different from the bloom periods in 2006 and 2008. The results of EOF analysis show its potential for long-term integrated lake monitoring, not only in Lake Taihu but also in other large lakes threatened by accelerating eutrophication.     

Hippocampal Long-Term Potentiation Attenuated by Lesions in the Marginal Division of Neostriatum

The marginal division (MrD) is a spindled-neurons consisted zone at the caudal border of the neostriatum in the mammalian brain and has been verified as contributing to associative learning and declarative memory in the rat and human with behavior and functional magnetic resonance imaging methods. It was proved to have functional connections with the limbic system. Whether the MrD has influence on the hippocampal long-term potentiation (LTP) was investigated in this study. LTP was induced from the dentate gyrus (DG) in the hippocampus by high-frequency stimulation (HFS) to the perforant path (PP). The amplitude of the population spike (PS) and the slope of the excitatory postsynaptic potential (EPSP) increased significantly to form LTP in the DG of the hippocampus after HFS of PP in normal and saline-injected control groups of rats. Lesions introduced in the MrD reduced significantly both the amplitude of PS and the slope of the EPSP following HFS of the PP. The results indicated that lesions in the MrD could attenuate LTP formation in the hippocampus. Our data suggest that the MrD might very possibly have excitatory functional influence on the hippocampus and therefore might influence the function of the hippocampus.     

Removal of highly elevated nitrate from drinking water by pH-heterogenized heterotrophic denitrification facilitated with ferrous sulfide-based autotrophic denitrification

The performance of acetic acid-supported pH-heterogenized heterotrophic denitrification (HD) facilitated with ferrous sulfide-based autotrophic denitrification (AD) was investigated in upflow activated carbon-packed column reactors for reliable removal of highly elevated nitrate (42 mg NO₃-N l⁻¹) in drinking water. The use of acetic acid as substrate provided sufficient internal carbon dioxide to completely eliminate the need of external pH adjustment for HD, but simultaneously created vertically heterogenized pH varying from 4.8 to 7.8 in the HD reactor. After 5-week acclimation, the HD reactor developed a moderate nitrate removal capacity with about one third of nitrate removal occurring in the acidic zone (pH 4.8–6.2). To increase the treatment reliability, acetic acid-supported HD was operated under 10% carbon limitation to remove >85% of nitrate, and ferrous sulfide-based AD was supplementally operated to remove residual nitrate and formed nitrite without excess of soluble organic carbon, nitrite or sulfate in the final effluent.     

Temperature Response of Soil Respiration in a Chinese Pine Plantation: Hysteresis and Seasonal vs. Diel Q 10

Although the temperature response of soil respiration (R_s) has been studied extensively, several issues remain unresolved, including hysteresis in the R_s–temperature relationship and differences in the long- vs. short-term R_s sensitivity to temperature. Progress on these issues will contribute to reduced uncertainties in carbon cycle modeling. We monitored soil CO₂ efflux with an automated chamber system in a Pinus tabulaeformis plantation near Beijing throughout 2011. Soil temperature at 10-cm depth (T_s) exerted a strong control over R_s, with the annual temperature sensitivity (Q ₁₀) and basal rate at 10°C (R_{s 10}) being 2.76 and 1.40 µmol m⁻² s⁻¹, respectively. Both R_s and short-term (i.e., daily) estimates of R_{s 10} showed pronounced seasonal hysteresis with respect to T_s, with the efflux in the second half of the year being larger than that early in the season for a given temperature. The hysteresis may be associated with the confounding effects of microbial population dynamics and/or litter input. As a result, all of the applied regression models failed to yield unbiased estimates of R_s over the entire annual cycle. Lags between R_s and T_s were observed at the diel scale in the early and late growing season, but not in summer. The seasonality in these lags may be due to the use of a single T_s measurement depth, which failed to represent seasonal changes in the depth of CO₂ production. Daily estimates of Q ₁₀ averaged 2.04, smaller than the value obtained from the seasonal relationship. In addition, daily Q ₁₀ decreased with increasing T_s, which may contribute feedback to the climate system under global warming scenarios. The use of a fixed, universal Q ₁₀ is considered adequate when modeling annual carbon budgets across large spatial extents. In contrast, a seasonally-varying, environmentally-controlled Q ₁₀ should be used when short-term accuracy is required.