MicroRNA 421 suppresses DPC4/Smad4 in pancreatic cancer

Dihydroavenanthramide D (DHAvD) is a synthetic analog to naturally occurring avenanthramide, which is the active component of oat. Previous study demonstrates that DHAvD strongly inhibits activation of nuclear factor-kappa B (NF-κB), which is a major component in cancer cell invasion. The present study investigated whether DHAvD can modulate MMP-9 expression and cell invasion in MCF-7 human breast cancer cells. MMP-9 expression and cell invasion in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) was increased, whereas these inductions were muted by DHAvD. DHAvD also suppressed activation of mitogen-activated protein kinase (MAPK), and MAPK-mediated nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) activations in TPA-treated MCF-7 cells. The results indicate that DHAvD-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the MAPK/NF-κB and MAPK/AP-1 pathways in MCF-7 cells. DHAvD may have potential value in breast cancer metastasis.     

MicroRNA 421 suppresses DPC4/Smad4 in pancreatic cancer

MicroRNAs (miRNAs) have emerged as important regulators in the development of pancreatic cancer and may be a valuable therapeutic application. DPC4/Smad4 is a critical tumor suppressor involved in the progression of pancreatic cancer, but few studies have been conducted to determine its relationship with miRNAs. In this study, we identify miR-421 as a potential regulator of DPC4/Smad4. We find that in human clinical specimens of pancreatic cancer miR-421 is aberrantly upregulated while DPC4/Smad4 is strongly repressed, and their levels of expression are inversely correlated. Moreover, ectopic expression of miR-421 significantly decreases DPC4/Smad4 protein level in pancreatic cancer cell lines and simultaneously promotes cell proliferation and colony formation in vitro. Our findings identify miR-421 as a potent regulator of DPC4/Smad4, which may provide a novel therapeutic strategy for treatment of DPC4/Smad4-driven pancreatic cancer.     

Complete genome sequence of Mycoplasma hyopneumoniae strain 168

Mycoplasma hyopneumoniae strain 168, a pathogenic strain prevalent in China, was isolated in 1974. Although this strain has been widespread for a long time, the genome sequence had not been determined. Here, we announce the complete genome sequence of M. hyopneumoniae strain 168.     

The reduction of food web robustness by parasitism: fact and artefact

A robust food web is one which suffers few secondary extinctions after primary species losses. While recent research has shown that a food web with parasitism is less robust than one without, it still remains unclear whether the reduction in robustness is due to changes in network complexity or unique characteristics associated with parasitism. Here, using several published food webs, simulation experiments with different food web models and extinction scenarios were conducted to elucidate how such reduction can be achieved. Our results show that, regardless of changes in network complexity and preferential parasitism, the reduction in food web robustness is mainly due to the life cycle constraint of parasites. Our findings further demonstrate that parasites are prone to secondary extinctions and that their extinctions occur earlier than those involving free-living species. These findings suggest that the vulnerable nature of parasites to species loss makes them highly sensitive indicators of food web integrity.     

Enzyme inactivation by ethanol and development of a kinetic model for thermophilic simultaneous saccharification and fermentation at 50 °C with Thermoanaerobacterium saccharolyticum ALK2

Studies were undertaken to understand phenomena operative during simultaneous saccharification and fermentation (SSF) of a model cellulosic substrate (Avicel) at 50°C with enzymatic hydrolysis mediated by a commercial cellulase preparation (Spezyme CP) and fermentation by a thermophilic bacterium engineered to produce ethanol at high yield, Thermoanaerobacterium saccharolyticum ALK2. Thermal inactivation at 50 °C, as shown by the loss of 50% of enzyme activity over 4 days in the absence of ethanol, was more severe than at 37 °C, where only 25% of enzyme activity was lost. In addition, at 50 °C ethanol more strongly influenced enzyme stability. Enzyme activity was moderately stabilized between ethanol concentrations of 0 and 40 g/L, but ethanol concentrations above 40 g/L accelerated enzyme inactivation, leading to 75% loss of enzymatic activity in 80 g/L ethanol after 4 days. At 37 °C, ethanol did not show a strong effect on the rate of enzyme inactivation. Inhibition of cellulase activity by ethanol, measured at both temperatures, was relatively similar, with the relative rate of hydrolysis inhibited 50% at ethanol concentrations of 56.4 and 58.7 g/L at 50 and 37 °C, respectively. A mathematical model was developed to test whether the measured phenomena were sufficient to quantitatively describe system behavior and was found to have good predictive capability at initial Avicel concentrations of 20 and 50 g/L.     

Increased expression of mGITRL on D2SC/1 cells by particulate β-glucan impairs the suppressive effect of CD4+CD25+ regulatory T cells and enhances the effector T cell proliferation

β-Glucans have been shown to enhance immune responses for centuries, which contributes to their anti-tumor property. However, their mechanisms of action are still elusive. Dectin-1, the C-type lectin receptor for β-glucan, is expressed abundantly on dendritic cells (DCs). Activation of DCs via Dectin-1 can lead to the maturation of DC, inducing both innate and adaptive immune responses against tumor development and microbial infection. In this study, we found that particulate yeast-derived β-glucans could induce the maturation of murine dendritic cell line D2SC/1 cells and increase the expression of mGITRL on D2SC/1 cells via Dectin-1/Syk pathway in a dose dependent manner. Furthermore, we demonstrated that the increased mGITRL on D2SC/1 cells could impair the suppressive activity of CD4⁺CD25⁺ regulatory T cells (Tregs) and enhance the proliferation of CD4⁺CD25⁻ effector T cells (Teffs). These findings suggest that particulate β-glucan can be used as immunomodulator to stimulate potent T cell-mediated adaptive immunity while down-regulate immune suppressive activity, leading to a more efficient defense mechanism against tumor development or infectious diseases.     

Strong plant-soil associations in a heterogeneous subtropical broad-leaved forest

The relative importance of deterministic and neutral processes on community assembly is currently a topic of much debate among ecologists. Analyzing species-environment associations is an effective way to assess the importance of deterministic process such as niche differentiation, but both habitat association and dispersal limitation can produce similar patterns of spatial aggregation in species. Therefore, it is crucial to control for the impact of dispersal limitation on species distributions when analyzing species-environment associations. We sampled soil with high resolutions in a 24 ha stem-mapped subtropical forest and tested plant-soil associations. We controlled for the influence of dispersal limitation by employing the homogeneous Thomas process to simulate the effect of dispersal limitation on the aggregation of tree species. After controlling for the effect of dispersal limitation, we found that the spatial heterogeneity of soil properties was associated with distributions of 88.2% (90 of 102 species) of tree species in this subtropical forest. Furthermore, not only did soil properties influence the distribution of tree species, but also tree species tended to affect properties of the soil around them. The soil factors most strongly influencing species distributions were TC, TN, TP, K, Mg, Si, soil moisture, and bulk density. We found the spatial heterogeneity of soil properties to be strongly associated with tree species distributions. Niche partitioning of soil gradients contributed substantially to species coexistence in this subtropical forest.