A novel arabinose-inducible genetic operation system developed for Clostridium cellulolyticum

<p> Background: Clostridium cellulolyticum and other cellulolytic Clostridium strains are natural producers of lignocellulosic biofuels and chemicals via the consolidated bioprocessing (CBP) route, and systems metabolic engineering is indispensable to meet the cost-efficient demands of industry. Several genetic tools have been developed for Clostridium strains, and an efficient and stringent inducible genetic operation system is still required for the precise regulation of the target gene function.</p

High expression of transcriptional coactivator p300 correlates with aggressive features and poor prognosis of hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>It has been suggested that p300 participates in the regulation of a wide range of cell biological processes and mutation of p300 has been identified in certain types of human cancers. However, the expression dynamics of p300 in hepatocellular carcinoma (HCC) and its clinical/prognostic significance are unclear.</p> <p>Methods</p> <p>In this study, the methods of reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry (IHC) were utilized to investigate protein/mRNA expression of p300 in HCCs. Receiver operating characteristic (ROC) curve analysis, spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data.</p> <p>Results</p> <p>Up-regulated expression of p300 mRNA and protein was observed in the majority of HCCs by RT-PCR and Western blotting, when compared with their adjacent non-malignant liver tissues. According to the ROC curves, the cutoff score for p300 high expression was defined when more than 60% of the tumor cells were positively stained. High expression of p300 was examined in 60/123 (48.8%) of HCCs and in 8/123 (6.5%) of adjacent non-malignant liver tissues. High expression of p300 was correlated with higher AFP level, larger tumor size, multiplicity, poorer differentiation and later stage (<it>P </it>< 0.05). In univariate survival analysis, a significant association between overexpression of p300 and shortened patients' survival was found (<it>P </it>= 0.001). In different subsets of HCC patients, p300 expression was also a prognostic indicator in patients with stage II (<it>P </it>= 0.007) and stage III (<it>P </it>= 0.011). Importantly, p300 expression was evaluated as an independent prognostic factor in multivariate analysis (<it>P </it>= 0.021). Consequently, a new clinicopathologic prognostic model with three poor prognostic factors (p300 expression, AFP level and vascular invasion) was constructed. The model could significantly stratify risk (low, intermediate and high) for overall survival (<it>P </it>< 0.0001).</p> <p>Conclusions</p> <p>Our findings provide a basis for the concept that high expression of p300 in HCC may be important in the acquisition of an aggressive phenotype, suggesting that p300 overexpression, as examined by IHC, is an independent biomarker for poor prognosis of patients with HCC. The combined clinicopathologic prognostic model may become a useful tool for identifying HCC patients with different clinical outcomes.</p

L-Cysteine-Derived H2S Promotes Microglia M2 Polarization via Activation of the AMPK Pathway in Hypoxia-Ischemic Neonatal Mice

We have reported previously that L-cysteine-derived hydrogen sulfide (H2S) demonstrates a remarkable neuroprotective effect against hypoxia-ischemic (HI) insult in neonatal animals. Here, we assessed some of the mechanisms of this protection as exerted by L-cysteine. Specifically, we examined the capacity for L-cysteine to stimulate microglial polarization of the M2 phenotype and its modulation of complement expression in response to HI in neonatal mice. L-cysteine treatment suppressed the production of inflammatory cytokines, while dramatically up-regulating levels of anti-inflammatory cytokines in the damaged cortex. This L-cysteine administration promoted the conversion of microglia from an inflammatory M1 to an anti-inflammatory M2 phenotype, an effect which was associated with inhibiting the p38 and/or JNK pro-inflammatory pathways, nuclear factor-κB activation and a decrease in HI-derived levels of the C1q, C3a and C3a complement receptor proteins. Notably, blockade of H2S-production clearly prevented L-cysteine-mediated M2 polarization and complement expression. L-cysteine also inhibited neuronal apoptosis as induced by conditioned media from activated M1 microglia in vitro. We also show that L-cysteine promoted AMP-activated protein kinase (AMPK) activation and the AMPK inhibitor abolished these anti-apoptotic and anti-inflammatory effects of L-cysteine. Taken together, our findings demonstrate that L-cysteine-derived H2S attenuated neuronal apoptosis after HI and suggest that these effects, in part, result from enhancing microglia M2 polarization and modulating complement expression via AMPK activation

The contribution of cellulosomal scaffoldins to cellulose hydrolysis by Clostridium thermocellum analyzed by using thermotargetrons

<p> Background: Clostridium thermocellum is a thermophilic anaerobic bacterium that degrades cellulose by using a highly effective cellulosome, a macromolecular complex consisting of multiple cellulose degrading enzymes organized and attached to the cell surface by non-catalytic scaffoldins. However, due largely to lack of efficient methods for genetic manipulation of C. thermocellum, it is still unclear how the different scaffoldins and their functional modules contribute to cellulose hydrolysis.</p

Electrical switching of ferro-rotational order in nano-thick 1T-TaS2_2 crystals

Hysteretic switching of domain states is a salient character of all ferroic materials and the foundation for their multifunctional applications. Ferro-rotational order is emerging as a new type of ferroic order featuring structural rotations, but its controlled switching remains elusive due to its invariance under both time reversal and spatial inversion. Here, we demonstrate electrical switching of ferro-rotational domain states in nanometer-thick 1T-TaS$_2$ crystals in its charge-density-wave phases. Cooling from the high-symmetry phase to the ferro-rotational phase under an external electric field induces domain state switching and domain wall formation, realized in a simple two-terminal configuration using a volt-scale voltage. Although the electric field does not couple with the order due to symmetry mismatch, it drives domain wall propagation to give rise to reversible, durable, and nonvolatile isothermal state switching at room temperature. These results pave the path for manipulation of the ferro-rotational order and its nanoelectronic applications