The use of plant biomass for biofuel production will require efficient utilization of the sugars in lignocellulose, primarily glucose and xylose. However, strains of Saccharomyces cerevisiae ...presently used in bioethanol production ferment glucose but not xylose. Yeasts engineered to ferment xylose do so slowly, and cannot utilize xylose until glucose is completely consumed. To overcome these bottlenecks, we engineered yeasts to coferment mixtures of xylose and cellobiose. In these yeast strains, hydrolysis of cellobiose takes place inside yeast cells through the action of an intracellular β-glucosidase following import by a high-affinity cellodextrin transporter. Intracellular hydrolysis of cellobiose minimizes glucose repression of xylose fermentation allowing coconsumption of cellobiose and xylose. The resulting yeast strains, cofermented cellobiose and xylose simultaneously and exhibited improved ethanol yield when compared to fermentation with either cellobiose or xylose as sole carbon sources. We also observed improved yields and productivities from cofermentation experiments performed with simulated cellulosic hydrolyzates, suggesting this is a promising cofermentation strategy for cellulosic biofuel production. The successful integration of cellobiose and xylose fermentation pathways in yeast is a critical step towards enabling economic biofuel production.
Mesoporous n-type hematite bunched nanowires (α-Fe2O3 BNWs) and Zn-, In- and Sn-doped α-Fe2O3 BNWs were synthesized by nanocasting method, and then the influence of the different-valence ...metals-doping on the microstructures, components and gas-sensing properties is discussed in detail. All samples present mesoporous-structure and are composed of the uniform α-Fe2O3 nanowires. The Zn, Fe, Sn and In-doped concentration decreased with the increasing radius of their hydrated ions. The ethanol gas-sensing results indicate that the different-valence metals-doping greatly affects the response of α-Fe2O3 BNWs sensors to ethanol gas. The sensitivity to 100 ppm ethanol gas increased from 10.046 for Fe1.896Zn0.104O2.948 BNWs sensor up to 45.556 for Fe1.938Sn0.062O3.031 BNWs sensor with the increasing metal valence. The high-valence Sn-doping not only decreases the ground state resistance, but also reduces barrier and work function of α-Fe2O3 BNWs, which results in the improved the sensitivity of α-Fe2O3 BNWs.
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•All samples present mesoporous-structure with the similar microstructures.•The doped concentration decreased with the increasing radius of their hydrated ions.•Metal-doping greatly affects the resistance and the gas-sensing properties of all sensors.•The high-valence doping reduces barrier and work function of α-Fe2O3 BNWs.•The Sn-doping supplies more inner electron and adsorbs more O− at surface in air.
The amyloid-β protein (Aβ) protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). It is believed that Aβ deposited in the brain originates from the brain tissue itself. ...However, Aβ is generated in both brain and peripheral tissues. Whether circulating Aβ contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human Aβ originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aβ plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aβ accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived Aβ can enter the brain, form the Aβ-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting Aβ metabolism in both the brain and the periphery.
In this paper, the prediction skills of five ensemble methods for temperature and precipitation are discussed by considering 20 yr of simulation results (from 1989 to 2008) for four regional climate ...models (RCMs) driven by NCEP–Department of Energy and ECMWF Interim Re-Analysis (ERA-Interim) boundary conditions. The simulation domain is the Coordinated Regional Downscaling Experiment (CORDEX) for East Asia, and the number of grid points is 197 × 233 with a 50-km horizontal resolution. Three new performance-based ensemble averaging (PEA) methods are developed in this study using 1) bias, root-mean-square errors (RMSEs) and absolute correlation (PEA_BRC), RMSE and absolute correlation (PEA_RAC), and RMSE and original correlation (PEA_ROC). The other two ensemble methods are equal-weighted averaging (EWA) and multivariate linear regression (Mul_Reg). To derive the weighting coefficients and cross validate the prediction skills of the five ensemble methods, the authors considered 15-yr and 5-yr data, respectively, from the 20-yr simulation data. Among the five ensemble methods, the Mul_Reg (EWA) method shows the best (worst) skill during the training period. The PEA_RAC and PEA_ROC methods show skills that are similar to those of Mul_Reg during the training period. However, the skills and stabilities of Mul_Reg were drastically reduced when this method was applied to the prediction period. But, the skills and stabilities of PEA_RAC were only slightly reduced in this case. As a result, PEA_RAC shows the best skill, irrespective of the seasons and variables, during the prediction period. This result confirms that the new ensemble method developed in this study, PEA_RAC, can be used for the prediction of regional climate.
We report microporous carbon nanosheets containing numerous redox active heteroatoms fabricated from exfoliated waste coffee grounds by simple heating with KOH for pseudocapacitive charge storage. We ...found that various heteroatom combinations in carbonaceous materials can be a redox host for lithium ion storage. The bio-inspired nanomaterials had unique characteristics, showing superior electrochemical performances as cathode for asymmetric pseudocapacitors.
Aim To assess the utility of dual-source dual-energy computed tomography angiography (DSDECTA) in the diagnosis of active gastrointestinal bleeding (GIB). Materials and methods From June 2010 to ...September 2011, 58 consecutive patients with clinical signs of active GIB underwent DSDECTA. Two radiologists, blinded to clinical data, interpreted images from DSDECTA independently, with discordant interpretation resolved by consensus. The standards of reference included digital subtraction angiography, endoscopy, surgery, or final pathology reports. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy of DSDECTA for detection of active GIB were evaluated. Receiver-operating characteristic (ROC) analysis was undertaken and the area under the curve (AUC) calculated. Results Active GIB source was identified in 39 of 58 patients (67.2%), all of which were confirmed by one or more reference standard. Negative DSDECTA results were obtained in 19 patients (32.8%). Of these, 15 patients did not require any further intervention and were discharged without incident. The overall sensitivity, specificity, PPV, NPV, and accuracy of DSDECTA was 88.6, 100, 100, 73.7, and 91.4%, respectively. The AUC was 0.935 ± 0.063. The dose reduction of a dual-phase DSDECTA protocol was approximately 30%, compared with that of a triple-phase protocol used in a previous study. Conclusion DSDECTA can act as an accurate method for detection and localization of active GIB and has a relatively low radiation dose.
The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 10
electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV ...energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays
. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref.
). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane
, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.
To investigate the anti-obesity effect of Rubi Fructus (RF) extract using brown adipose tissue (BAT) and primary brown preadipocytes in vivo and in vitro.
Male C57BL/6 J mice (n=5 per group) were fed ...a high-fat diet (HFD) for 10 weeks with or without RF. Brown preadipocytes from the interscapular BAT of mice (age, post-natal days 1-3) were cultured with differentiation media (DM) including isobutylmethylxanthine, dexamethasone, T3, indomethacin and insulin with or without RF.
In HFD-induced obese C57BL/6 J mice, long-term RF treatment significantly reduced weight gain as well as the weights of the white adipose tissue, liver and spleen. Serum levels of total cholesterol and low-density lipoprotein cholesterol were also reduced in the HFD group which received RF treatment. Furthermore, RF induced thermogenic-, adipogenic- and mitochondria-related gene expressions in BAT. In primary brown adipocytes, RF effectively stimulated the expressions of thermogenic- and mitochondria-related genes. In addition, to examine whether LIPIN1, a regulator of adipocyte differentiation, is regulated by RF, Lipin1 small interfering RNA (siRNA) and RF were pretreated in primary brown adipocytes. Pretreatment with Lipin1 siRNA and RF downregulated the DM-induced expression levels of thermogenic- and mitochondria-related genes. Moreover, RF markedly upregulated AMP-activated protein kinase. Our study shows that RF is capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes.
This study demonstrates that RF prevents the development of obesity in mice fed with a HFD and that it is also capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes, which suggests that RF has potential as a therapeutic application for the treatment or prevention of obesity.
Industrial polyploid yeast strains harbor numerous beneficial traits but suffer from a lack of available auxotrophic markers for genetic manipulation. Here we demonstrated a quick and efficient ...strategy to generate auxotrophic markers in industrial polyploid yeast strains with the RNA-guided Cas9 nuclease. We successfully constructed a quadruple auxotrophic mutant of a popular industrial polyploid yeast strain, Saccharomyces cerevisiae ATCC 4124, with ura3, trp1, leu2, and his3 auxotrophies through RNA-guided Cas9 nuclease. Even though multiple alleles of auxotrophic marker genes had to be disrupted simultaneously, we observed knockouts in up to 60% of the positive colonies after targeted gene disruption. In addition, growth-based spotting assays and fermentation experiments showed that the auxotrophic mutants inherited the beneficial traits of the parental strain, such as tolerance of major fermentation inhibitors and high temperature. Moreover, the auxotrophic mutants could be transformed with plasmids containing selection marker genes. These results indicate that precise gene disruptions based on the RNA-guided Cas9 nuclease now enable metabolic engineering of polyploid S. cerevisiae strains that have been widely used in the wine, beer, and fermentation industries.
L-ascorbate (L-ascorbic acid, vitamin C) clearly has an inhibitory effect on cancer cells. However, the mechanism underlying differential sensitivity of cancer cells from same tissue to L-ascorbate ...is yet to be clarified. Here, we demonstrate that L-ascorbate has a selective killing effect, which is influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human breast cancer cells. Treatment of human breast cancer cells with L-ascorbate differentially induced cell death, dependent on the SVCT-2 protein level. Moreover, knockdown of endogenous SVCT-2 via RNA interference in breast cancer cells expressing high levels of the protein induced resistance to L-ascorbate treatment, whereas transfection with SVCT-2 expression plasmids led to enhanced L-ascorbate chemosensitivity. Surprisingly, tumor regression by L-ascorbate administration in mice bearing tumor cell xenograft also corresponded to the SVCT-2 protein level. Interestingly, SVCT-2 expression was absent or weak in normal tissues, but strongly detected in tumor samples obtained from breast cancer patients. In addition, enhanced chemosensitivity to L-ascorbate occurred as a result of caspase-independent autophagy, which was mediated by beclin-1 and LC3 II. In addition, treatment with N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger, suppressed the induction of beclin-1 and LC3 II, implying that the differential SVCT-2 protein-dependent L-ascorbate uptake was attributable to intracellular ROS induced by L-ascorbate, subsequently leading to autophagy. These results suggest that functional SVCT-2 sensitizes breast cancer cells to autophagic damage by increasing the L-ascorbate concentration and intracellular ROS production and furthermore, SVCT-2 in breast cancer may act as an indicator for commencing L-ascorbate treatment.
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