Extract of Zanthoxylum bungeanum maxim seed oil reduces hyperlipidemia in hamsters fed high-fat diet via activation of peroxisome proliferator-activated receptor γ

Purpose: To investigate the anti-hyperlipidaemic effect of extract of Zanthoxylum bungeanum Maxim. seed oil (EZSO) on high-fat diet (HFD)-induced hyperlipidemic hamsters.Methods: Following feeding with HFD for 30 days, hyperlipidemic hamsters were intragastrically treated with EZSO for 60 days. Serum levels of triglyceride (TG), total cholesterol (TC), low-density-lipoproteincholesterol (LDL-C), nitric oxide (NO) and malondialdehyde (MDA) were analyzed. Protein expression and location of peroxisome proliferator-activated receptor γ (PPARγ) in liver were determined by Western blot and immunohistochemical assays, respectively.Results: EZSO at 5 and 10 g/kg significantly reduced levels of TG by 26 and 23 % (p < 0.05), TC by 19 % (p < 0.01) and 13 % (p < 0.01), LDL-C by 18 % (p < 0.05) and 21 % (p < 0.01), NO by 15 % (p < 0.01) and 31 % (p < 0.01), and MDA by 16 % (p < 0.05) and 30 % (p < 0.01), respectively, in serum of hyperlipidemic hamsters. However, EZSO did not show significant effect on HDL-C level in serum. Furthermore, EZSO at 5 and 10 g/kg markedly promoted protein expression of PPARγ by 71 % (p < 0.05) and 102 % (p < 0.01) in liver tissue of hyperlipidemic hamsters. EZSO also notably increased the content of PPARγ protein in the nucleus of liver cells of hyperlipidemic hamsters.Conclusion: These findings suggest that EZSO can reduce hyperlipidemia and improve oxidative stress in hyperlipidemic hamsters through activation of PPARγ, and that EZSO is a promising novel hypolipidemic health product.Keywords: Zanthoxylum bungeanum, Peroxisome proliferator activated receptor γ, Hyperlipidemia, Hamster, High-fat die

Regulation of gamete release in the economic brown seaweed Hizikia fusiforme (Phaeophyta)

Gamete release is an essential event in artificial seeding of the economic brown seaweed, Hizikia fusiforme. Mass egg release occurred in the dark, with few eggs being discharged in the light. Release of eggs was elicited with eight practical salinity units (one PSU = 1 g sea salts l(-1)) and was inhibited by salinity levels > 32 PSU. Egg release was optimal at 23 degrees C, and was decreased by 72% in agitated seawater compared to unstirred seawater. Inhibitors of photosynthesis and ions channels suppressed egg release, indicating that this process was physiologically associated with photosynthetic activity and ion transport.Gamete release is an essential event in artificial seeding of the economic brown seaweed, Hizikia fusiforme. Mass egg release occurred in the dark, with few eggs being discharged in the light. Release of eggs was elicited with eight practical salinity units (one PSU = 1 g sea salts l(-1)) and was inhibited by salinity levels > 32 PSU. Egg release was optimal at 23 degrees C, and was decreased by 72% in agitated seawater compared to unstirred seawater. Inhibitors of photosynthesis and ions channels suppressed egg release, indicating that this process was physiologically associated with photosynthetic activity and ion transport

Single-cell bacterial transcription measurements reveal the importance of dimethylsulfoniopropionate (DMSP) hotspots in ocean sulfur cycling.

Dimethylsulfoniopropionate (DMSP) is a pivotal compound in marine biogeochemical cycles and a key chemical currency in microbial interactions. Marine bacteria transform DMSP via two competing pathways with considerably different biogeochemical implications: demethylation channels sulfur into the microbial food web, whereas cleavage releases sulfur into the atmosphere. Here, we present single-cell measurements of the expression of these two pathways using engineered fluorescent reporter strains of Ruegeria pomeroyi DSS-3, and find that external DMSP concentration dictates the relative expression of the two pathways. DMSP induces an upregulation of both pathways, but only at high concentrations (>1 μM for demethylation; >35 nM for cleavage), characteristic of microscale hotspots such as the vicinity of phytoplankton cells. Co-incubations between DMSP-producing microalgae and bacteria revealed an increase in cleavage pathway expression close to the microalgae's surface. These results indicate that bacterial utilization of microscale DMSP hotspots is an important determinant of the fate of sulfur in the ocean

Phosphorylation of the androgen receptor is associated with reduced survival in hormonerefractory prostate cancer patients

Cell line studies demonstrate that the PI3K/Akt pathway is upregulated in hormone-refractory prostate cancer (HRPC) and can result in phosphorylation of the androgen receptor (AR). The current study therefore aims to establish if this has relevance to the development of clinical HRPC. Immunohistochemistry was employed to investigate the expression and phosphorylation status of Akt and AR in matched hormone-sensitive and -refractory prostate cancer tumours from 68 patients. In the hormone-refractory tissue, only phosphorylated AR (pAR) was associated with shorter time to death from relapse (<i>P</i>=0.003). However, when an increase in expression in the transition from hormone-sensitive to -refractory prostate cancer was investigated, an increase in expression of PI3K was associated with decreased time to biochemical relapse (<i>P</i>=0.014), and an increase in expression of pAkt<sup>473</sup> and pAR<sup>210</sup> were associated with decreased disease-specific survival (<i>P</i>=0.0019 and 0.0015, respectively). Protein expression of pAkt<sup>473</sup> and pAR<sup>210</sup> also strongly correlated (<i>P</i><0.001, c.c.=0.711) in the hormone-refractory prostate tumours. These results provide evidence using clinical specimens, that upregulation of the PI3K/Akt pathway is associated with phosphorylation of the AR during development of HRPC, suggesting that this pathway could be a potential therapeutic target

Requirement of CRTC1 coactivator for hepatitis B virus transcription

Transcription of hepatitis B virus (HBV) from the covalently closed circular DNA (cccDNA) template is essential for its replication. Suppressing the level and transcriptional activity of cccDNA might have anti-HBV effect. Although cellular transcription factors, such as CREB, which mediate HBV transcription, have been well described, transcriptional coactivators that facilitate this process are incompletely understood. In this study we showed that CREB-regulated transcriptional coactivator 1 (CRTC1) is required for HBV transcription and replication. The steady-state levels of CRTC1 protein were elevated in HBV-positive hepatoma cells and liver tissues. Ectopic expression of CRTC1 or its homolog CRTC2 or CRTC3 in hepatoma cells stimulated the activity of the preS2/S promoter of HBV, whereas overexpression of a dominant inactive form of CRTC1 inhibited HBV transcription. CRTC1 interacts with CREB and they are mutually required for the recruitment to the preS2/S promoter on cccDNA and for the activation of HBV transcription. Accumulation of pregenomic RNA (pgRNA) and cccDNA was observed when CRTC1 or its homologs were overexpressed, whereas the levels of pgRNA, cccDNA and secreted HBsAg were diminished when CRTC1 was compromised. In addition, HBV transactivator protein HBx stabilized CRTC1 and promoted its activity on HBV transcription. Our work reveals an essential role of CRTC1 coactivator in facilitating and supporting HBV transcription and replication.published_or_final_versio

Basic Amino Acid Mutations in the Nuclear Localization Signal of Hibiscus Chlorotic Ringspot Virus p23 Inhibit Virus Long Distance Movement

10.1371/journal.pone.0074000PLoS ONE89-POLN

Deep Sequencing of Small RNAs in Tomato for Virus and Viroid Identification and Strain Differentiation

Small RNAs (sRNA), including microRNAs (miRNA) and small interfering RNAs (siRNA), are produced abundantly in plants and animals and function in regulating gene expression or in defense against virus or viroid infection. Analysis of siRNA profiles upon virus infection in plant may allow for virus identification, strain differentiation, and de novo assembly of virus genomes. In the present study, four suspected virus-infected tomato samples collected in the U.S. and Mexico were used for sRNA library construction and deep sequencing. Each library generated between 5–7 million sRNA reads, of which more than 90% were from the tomato genome. Upon in-silico subtraction of the tomato sRNAs, the remaining highly enriched, virus-like siRNA pools were assembled with or without reference virus or viroid genomes. A complete genome was assembled for Potato spindle tuber viroid (PSTVd) using siRNA alone. In addition, a near complete virus genome (98%) also was assembled for Pepino mosaic virus (PepMV). A common mixed infection of two strains of PepMV (EU and US1), which shared 82% of genome nucleotide sequence identity, also could be differentially assembled into their respective genomes. Using de novo assembly, a novel potyvirus with less than 60% overall genome nucleotide sequence identity to other known viruses was discovered and its full genome sequence obtained. Taken together, these data suggest that the sRNA deep sequencing technology will likely become an efficient and powerful generic tool for virus identification in plants and animals

Entanglement of spin waves among four quantum memories

Quantum networks are composed of quantum nodes that interact coherently by way of quantum channels and open a broad frontier of scientific opportunities. For example, a quantum network can serve as a `web' for connecting quantum processors for computation and communication, as well as a `simulator' for enabling investigations of quantum critical phenomena arising from interactions among the nodes mediated by the channels. The physical realization of quantum networks generically requires dynamical systems capable of generating and storing entangled states among multiple quantum memories, and of efficiently transferring stored entanglement into quantum channels for distribution across the network. While such capabilities have been demonstrated for diverse bipartite systems (i.e., N=2 quantum systems), entangled states with N > 2 have heretofore not been achieved for quantum interconnects that coherently `clock' multipartite entanglement stored in quantum memories to quantum channels. Here, we demonstrate high-fidelity measurement-induced entanglement stored in four atomic memories; user-controlled, coherent transfer of atomic entanglement to four photonic quantum channels; and the characterization of the full quadripartite entanglement by way of quantum uncertainty relations. Our work thereby provides an important tool for the distribution of multipartite entanglement across quantum networks.Comment: 4 figure

Repeated growth and bubbling transfer of graphene with millimetre-size single-crystal grains using platinum

Large single-crystal graphene is highly desired and important for the applications of graphene in electronics, as grain boundaries between graphene grains markedly degrade its quality and properties. Here we report the growth of millimetre-sized hexagonal single-crystal graphene and graphene films joined from such grains on Pt by ambient-pressure chemical vapour deposition. We report a bubbling method to transfer these single graphene grains and graphene films to arbitrary substrate, which is nondestructive not only to graphene, but also to the Pt substrates. The Pt substrates can be repeatedly used for graphene growth. The graphene shows high crystal quality with the reported lowest wrinkle height of 0.8 nm and a carrier mobility of greater than 7,100 cm2 V−1 s−1 under ambient conditions. The repeatable growth of graphene with large single-crystal grains on Pt and its nondestructive transfer may enable various applications

Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel