JAB1 accelerates mitochondrial apoptosis by interaction with proapoptotic BclGs

The Bcl-2 family of proteins is the key regulators of cell apoptosis at the mitochondria level. The BH3-only pro-apoptotic member BclGs was unique among the family due to its highly specific expression in human testis and has been demonstrated to induce apoptosis dependent on the BH3 domain. However, the molecular mechanism of BclGs-induced apoptosis remains unclear. Here we show that overexpression of BclGs could induce Bax expression upregulation and translocation to mitochondria, cytochrome c release and activation of caspase-3. Moreover, we identified JAB1 as a novel BclGs-specific binding protein through a yeast two-hybrid screening in a human testis cDNA library. BclGs interacts with JAB1 both in vitro and in vivo. N-terminal region of BclGs (aa 1-67) was required for the interaction. Importantly, JAB1 and BclGs co-expression synergistically induces apoptosis. JAB1 could compete with Bcl-XL/Bcl-2 to bind to BclGs; thus, promote the apoptosis. RNAi-mediated knock-down of JAB1 results in the reduced proapoptotic activity of BclGs. Taken together, our results provided the first evidence that JAB1 is involved in the regulation of mitochondrial apoptotic pathway through specific interaction with BclGs.     

In Vitro Fabrication and Physicochemical Properties of a Hybrid Fibril from Xenogeneic Collagens

A Hybrid collagen fibril (HCF) assembled from xenogeneic collagens is a special kind of collagen fibrils in vivo and plays an important role in living systems. Inspired by nature, can a HCF form in vitro? Herein, we fabricated a new HCF by neutralizing a mixture of type I bullfrog (Rana catesbeiana Shaw) skin collagen and porcine (Sus scrofa domesticus) skin collagen with a phosphate buffer, and investigated its physicochemical properties. Self-assembly kinetics and fluorescence-quenching experiments showed that a significant intermolecular interaction and co-assembly behavior occurred between bullfrog skin collagen and porcine skin collagen, thus confirming that xenogeneic collagens can self-assemble to form HCF. Differential scanning calorimetry revealed that the thermal stability of HCF was completely different from that of the syngeneic bullfrog skin and porcine skin collagen fibrils. This finding indicated that a new kind of collagen fibril was fabricated successfully. Scanning electron microscopy and transmission electron microscopy tests showed that the diameters and D-periodicity lengths of HCF were smaller than those of the syngeneic collagen fibrils, suggesting that the morphological features of HCF were distinguished from those of the syngeneic fibril samples. Moreover, viscoelasticity of a collagen gel also changed after the self-assembly of xenogeneic collagens. Meanwhile, the obtained hybrid gel still exhibited good biocompatibility and cell proliferation properties. Finding from this work provides a new idea for the improvement or regulation of collagen-based products performance.     

Lagged climatic effects on carbon fluxes over three grassland ecosystems in China

Aims The plasticity of ecosystem responses could buffer and postpone the effects of climates on ecosystem carbon fluxes, but this lagged effect is often ignored. In this study, we used carbon flux data collected from three typical grassland ecosystems in China, including a temperate semiarid steppe in Inner Mongolia (Neimeng site, NM), an alpine shrub-meadow in Qinghai (Haibei site, HB) and an alpine meadow steppe in Tibet (Dangxiong site, DX), to examine the time lagged effects of environmental factors on CO₂ exchange.Methods Eddy covariance data were collected from three typical Chinese grasslands. In linking carbon fluxes with climatic factors, we used their averages or cumulative values within each 12-month period and we called them 'yearly' statistics in this study. To investigate the lagged effects of the climatic factors on the carbon fluxes, the climatic 'yearly' statistics were kept still and the 'yearly' statistics of the carbon fluxes were shifted backward 1 month at a time.Important findings Soil moisture and precipitation was the main factor driving the annual variations of carbon fluxes at the alpine HB and DX, respectively, while the NM site was under a synthetic impact of each climatic factor. The time lagged effect analysis showed that temperature had several months, even half a year lag effects on CO₂ exchange at the three studied sites, while moisture's effects were mostly exhibited as an immediate manner, except at NM. In general, the lagged climatic effects were relatively weak for the alpine ecosystem. Our results implied that it might be months or even 1 year before the variations of ecosystem carbon fluxes are adjusted to the current climate, so such lag effects could be resistant to more frequent climate extremes and should be a critical component to be considered in evaluating ecosystem stability. An improved knowledge on the lag effects could advance our understanding on the driving mechanisms of climate change effects on ecosystem carbon fluxes.     

Thymoquinone Suppresses the Proliferation,Migration and Invasiveness through Regulating ROS,Autophagic Flux and miR-877-5p in Human Bladder Carcinoma Cells

Bladder carcinoma is among the top 10 most frequently diagnosed cancer types in the world. As a phytochemical active metabolic, thymoquinone (TQ) is extracted from seeds of Nigella sativa, possessing various biological properties in a wide range of diseases. Moreover, the outstanding anti-cancer effect of TQ is attracting increasing attentions. In certain circumstances, moderate autophagy is regarded to facilitate the adaptation of malignant cells to different stressors. Conversely, closely linked with the mitochondrial membrane potential (MMP) loss, the upregulation of intracellular reactive oxygen species (ROS) is reported to activate the cell apoptosis in many cancer types. Furthermore, the vital effects of microRNAs in the pathological processes of cancer cells have also been confirmed by previous studies. The present research confirms that TQ restrains the viability, proliferation, migration and invasion through activating caspase-dependent apoptosis in bladder carcinoma cells, which is mediated by TQ induced ROS increase in bladder carcinoma cells. Furthermore, TQ is proved to block the fusion of autophagosomes and lysosomes, causing the accumulation of autophagosomes and subsequent cell apoptosis. In addition, TQ is also found to initiate the miR-877-5p/PD-L1 axis, which suppresses the epithelial mesenchymal transition (EMT) and invasion of bladder carcinoma cells. Taken together, TQ induces the apoptosis through upregulating ROS level and impairing autophagic flux, and inhibiting the EMT and cell invasion via activating the miR-877-5p/PD-L1 axis in bladder carcinoma cells.     

基于主成分分析的古树土壤肥力综合评价

以广州市海珠区登记在册的40株古树为研究对象,调查其生长状况,采集土壤测定pH、EC值、容重、通气度、有机质、全N、全P、全K、水解N、有效P、速效K含量等11项理化指标,采用主成分分析和聚类分析对古树土壤肥力进行综合评价.结果表明:海珠区大多数古树土壤EC值偏低(<0.35 mS·cm-1),表现为强变异;土壤有机质...     

Impact of road construction on giant panda’s habitat and its carrying capacity in Qinling Mountains

The Qinling giant panda (Ailuropoda melanoleuca) is an endangered endemic species to China. Despite ongoing efforts to ensure its conservation, concerns about maintaining its populations persist. We used GIS fed with data on land use including road network of 2001, third national giant panda survey, and a digital elevation model (DEM) to assess the impact of road construction on giant panda habitat, and estimate the carrying capacity of the Qinling Mountain area. We assessed habitat suitability with a mechanistic model, and conducted correlation analysis to evaluate relationship between the extent of giant panda habitat and amount of sites occupied by pandas within of 5 km × 5 km grid. We also estimated the carrying capacity of the Qinling Mountainous Area.
Our results revealed a significant correlation (R² = 0.447, P < 0.01) between the number of sites with signs left by giant panda and the extent of habitat within of 5 km × 5 km grid. The minimum habitat area that can support one panda was 10 km². Before the road network construction, the area of habitat suitable for the panda amounted about 1561 km² and that of marginally suitable habitat about 1499 km². The corresponding carrying capacity represented about 240 individuals. After the road network construction, the suitable habitat area was reduced by nearly 30% to 1093 km². Marginally suitable habitat and unsuitable habitat have both increased by 17% and 1%, respectively. As a result, the potential population size which the habitat could support was reduced to 217 individuals. The study results also suggested that most impacts on habitat from road construction took place in the high elevation areas above 1500 m. However, regarding the impact on the giant panda habitat, road networks developed much more inside the current nature reserves than outside of them.     

工业微生物的噬菌体感染与防治策略

以细菌为基础的生物技术在蓬勃发展的同时也不断受到噬菌体感染的威胁,噬菌体感染已成为微生物发酵过程中的一个顽疾,其实质是噬菌体与细菌之间复杂的共进化关系。在漫长的进化过程中,噬菌体已经形成了多种针对细菌抗性系统的逃逸机制。合理的工厂设计、菌株的轮换策略和传统的基因工程方法能在一定程度上降低噬菌体感染的风险,但仍然无法避免。基于CRISPR-Cas系统的防治策略仅需噬菌体的序列信息就可以理性设计噬菌体抗性菌株,且可以通过叠加效应不断增强菌种抗性,从而避免噬菌体的逃逸;群体感应信号分子则可以从整体水平上调节细菌的噬菌体抗性。这些新发现为噬菌体感染问题的解决带了新的希望,而噬菌体基因组编辑技术和合成生物学的快速发展则将进一步加深人们对噬菌体感染防治领域的认识。     

Modeling of Mitochondrial Donut Formation

Mitochondria are highly dynamic cell organelles. Continual cycles of fusion and fission play an important role in mitochondrial metabolism and cellular signaling. Previously, a novel mitochondrial morphology, the donut, was reported in cells after hypoxia-reoxygenation or osmotic pressure changes. However, the mechanism of donut formation remained elusive. Here, we obtained the distribution of donut diameters (D = 2R) and found that 95% are >0.8 μm. We also performed highly precise measurements of the mitochondrial tubule diameters using superresolution and electron microscopy. Then, we set up a model by calculating the mitochondrial bending energy and osmotic potential during donut formation. It shows that the bending energy is increased as the radius of curvature, R, gets smaller in the process of donut formation, especially for radii <0.4 μm, creating a barrier to donut formation. The calculations also show that osmotic potential energy release can balance the rising bending energy through volume expansion. Finally, we revealed the donut formation process in a Gibbs free-energy-dependent model combining calculations and measurements.     

Self-Assembling Nanoparticles Containing Dexamethasone as a Novel Therapy in Allergic Airways Inflammation

Nanocarriers can deliver a wide variety of drugs, target them to sites of interest, and protect them from degradation and inactivation by the body. They have the capacity to improve drug action and decrease undesirable systemic effects. We have previously developed a well-defined non-toxic PEG-dendritic block telodendrimer for successful delivery of chemotherapeutics agents and, in these studies, we apply this technology for therapeutic development in asthma. In these proof-of-concept experiments, we hypothesized that dexamethasone contained in self-assembling nanoparticles (Dex-NP) and delivered systemically would target the lung and decrease allergic lung inflammation and airways hyper-responsiveness to a greater degree than equivalent doses of dexamethasone (Dex) alone. We found that ovalbumin (Ova)-exposed mice treated with Dex-NP had significantly fewer total cells (2.78±0.44×10⁵ (n = 18) vs. 5.98±1.3×10⁵ (n = 13), P<0.05) and eosinophils (1.09±0.28×10⁵ (n = 18) vs. 2.94±0.6×10⁵ (n = 12), p<0.05) in the lung lavage than Ova-exposed mice alone. Also, lower levels of the inflammatory cytokines IL-4 (3.43±1.2 (n = 11) vs. 8.56±2.1 (n = 8) pg/ml, p<0.05) and MCP-1 (13.1±3.6 (n = 8) vs. 28.8±8.7 (n = 10) pg/ml, p<0.05) were found in lungs of the Dex-NP compared to control, and they were not lower in the Dex alone group. In addition, respiratory system resistance was lower in the Dex-NP compared to the other Ova-exposed groups suggesting a better therapeutic effect on airways hyperresponsiveness. Taken together, these findings from early-stage drug development studies suggest that the encapsulation and protection of anti-inflammatory agents such as corticosteroids in nanoparticle formulations can improve efficacy. Further development of novel drugs in nanoparticles is warranted to explore potential treatments for chronic inflammatory diseases such as asthma.