Changes in the Physical–Chemical Properties and Volatile Flavor Components of Dry-Cured Donkey Leg during Processing

In order to explore the quality variation and flavor formation of dry-cured donkey leg, the changes in physical-chemical composition, lipolytic, free amino acids content and volatile flavor compounds were investigated in this study. Six fresh, trimmed hind legs with average weight of 8.12 ± 0.8 kg were taken from male Dezhou donkeys slaughtered at the age of 24 months with the average live weight of 240 kg. The entire processing time was eight months long including six stages, specifically: cooling, salting, air-drying, fermenting and aging. Samples were collected at 0 d, 10 d, 20 d, 30 d, 65 d, 105 d and 165 d of processing. The results showed that the pH value remained stable in the range of 6.2~6.6. The moisture and water activity significantly decreased (p < 0.05) during processing. The chloride content, ash, total volatile basic nitrogen (TVB-N) and peroxide value (POV) significantly increased (p < 0.05), from 0.45% to 12.39%, from 3% to 17%, from 1.43 mg/kg to 8.98 mg/kg and from 1.39 g/100 g to 5.26 g/100 g, respectively. The thiobarbituric acid (TBARS) value reached its highest value of 0.39 mg MDA/kg at the end of the salting stage and then decreased to 0.34 mg MDA/kg. Eighteen free amino acids and fifteen free fatty acids were detected, and their contents were significantly increased during processing (p < 0.05). Volatile compounds were analyzed using solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS). Among 114 volatile compounds detected in dry-cured donkey leg, aldehydes, esters, alkane and alcohols were more abundant in the final products, with relative concentrations of 41.88%, 5.72%, 5.35% and 5.25%, respectively. Processing significantly affected the physical-chemical properties, which could contribute to the formation of flavor substances of dry-cured donkey leg

Salsolinol Facilitates Glutamatergic Transmission to Dopamine Neurons in the Posterior Ventral Tegmental Area of Rats

Although in vivo evidence indicates that salsolinol, the condensation product of acetaldehyde and dopamine, has properties that may contribute to alcohol abuse, the underlying mechanisms have not been fully elucidated. We have reported previously that salsolinol stimulates dopamine neurons in the posterior ventral tegmental area (p-VTA) partly by reducing inhibitory GABAergic transmission, and that ethanol increases glutamatergic transmission to VTA-dopamine neurons via the activation of dopamine D1 receptors (D1Rs). In this study, we tested the hypothesis that salsolinol stimulates dopamine neurons involving activation of D1Rs. By using whole-cell recordings on p-VTA-dopamine neurons in acute brain slices of rats, we found that salsolinol-induced increase in spike frequency of dopamine neurons was substantially attenuated by DL-2-amino-5-phosphono-valeric acid and 6, 7-dinitroquinoxaline-2, 3-dione, the antagonists of glutamatergic N-Methyl-D-aspartic acid and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Moreover, salsolinol increased the amplitude of evoked excitatory postsynaptic currents (EPSCs) and the frequency but not the amplitude of spontaneous EPSCs. Additionally, SKF83566, a D1R antagonist attenuated the salsolinol-induced facilitation of EPSCs and of spontaneous firing of dopamine neurons. Our data reveal that salsolinol enhances glutamatergic transmission onto dopamine neurons via activation of D1Rs at the glutamatergic afferents in dopamine neurons, which contributes to salsolinol's stimulating effect on p-VTA dopamine neurons. This appears to be a novel mechanism which contributes toward rewarding properties of salsolinol

Foreign patents surge and technology spillovers in China (1985-2009): evidence from the patent and trade markets

The paper investigates the determinants of foreign patent surge and the effects of technology spillovers in China based on an industry-level sample of 19 countries and regions from 1985 to 2009. We explore two hypotheses to explain the increasing foreign propensity to patent and the effects of technology spillovers in China, the market covering hypotheses and competitive threat hypotheses. The results show strong support for the competitive threat hypothesis. However, the foreign patenting surge in China does not mean China has more access to outsource advanced technology; on the contrary the technology spillover from foreign countries in China is limited. The paper investigates the determinants of foreign patent surge and the effects of technology spillovers in China based on an industry-level sample of 19 countries and regions from 1985 to 2009. We explore two hypotheses to explain the increasing foreign propensity to patent and the effects of technology spillovers in China, the market covering hypotheses and competitive threat hypotheses. The results show strong support for the competitive threat hypothesis. However, the foreign patenting surge in China does not mean China has more access to outsource advanced technology; on the contrary the technology spillover from foreign countries in China is limited

A bacteriophage-related chimeric marine virus infecting abalone

Extent: 12p.Marine viruses shape microbial communities with the most genetic diversity in the sea by multiple genetic exchanges and infect multiple marine organisms. Here we provide proof from experimental infection that abalone shriveling syndrome-associated virus (AbSV) can cause abalone shriveling syndrome. This malady produces histological necrosis and abnormally modified macromolecules (hemocyanin and ferritin). The AbSV genome is a 34.952-kilobase circular double-stranded DNA, containing putative genes with similarity to bacteriophages, eukaryotic viruses, bacteria and endosymbionts. Of the 28 predicted open reading frames (ORFs), eight ORF-encoded proteins have identifiable functional homologues. The 4 ORF products correspond to a predicted terminase large subunit and an endonuclease in bacteriophage, and both an integrase and an exonuclease from bacteria. The other four proteins are homologous to an endosymbiont-derived helicase, primase, single-stranded binding (SSB) protein, and thymidylate kinase, individually. Additionally, AbSV exhibits a common gene arrangement similar to the majority of bacteriophages. Unique to AbSV, the viral genome also contains genes associated with bacterial outer membrane proteins and may lack the structural protein-encoding ORFs. Genomic characterization of AbSV indicates that it may represent a transitional form of microbial evolution from viruses to bacteria.Jun Zhuang, Guiqin Cai, Qiying Lin, Zujian Wu and Lianhui Xi

Antitumor Efficacy of EGFR-Targeted Recombinant Immunotoxin in Human Head and Neck Squamous Cell Carcinoma

Over 90% of head and neck squamous cell carcinoma (HNSCC) overexpresses the epidermal growth factor receptor (EGFR). However, the EGFR-targeted monotherapy response rate only achieves 10–30% in HNSCC. Recombinant immunotoxin (RIT) often consists of an antibody targeting a tumor antigen and a toxin (e.g., diphtheria toxin [DT]) that kills cancer cells. We produced a humanized RIT, designated as hDT806, targeting overexpressed EGFR and investigated its effects in HNSCC. Distinct from the EGFR-targeted tyrosine kinase inhibitor erlotinib or antibody cetuximab, hDT806 effectively suppressed cell proliferation in the four HNSCC lines tested (JHU-011, -013, -022, and -029). In JHU-029 mouse xenograft models, hDT806 substantially reduced tumor growth. hDT806 decreased EGFR protein levels and disrupted the EGFR signaling downstream effectors, including MAPK/ERK1/2 and AKT, while increased proapoptotic proteins, such as p53, caspase-9, caspase-3, and the cleaved PAPR. The hDT806-induced apoptosis of HNSCC cells was corroborated by flow cytometric analysis. Furthermore, hDT806 resulted in a drastic inhibition in RNA polymerase II carboxy-terminal domain phosphorylation critical for transcription and a significant increase in the γH2A.X level, a DNA damage marker. Thus, the direct disruption of EGFR signaling, transcription inhibition, DNA damage, as well as apoptosis induced by hDT806 may contribute to its antitumor efficacy in HNSCC

Mitogen-activated protein kinase inhibition-induced modulation of epidermal growth factor receptor signaling in human head and neck squamous cell carcinoma

Background: Epidermal growth factor receptor (EGFR) overexpression is one of the most notable characteristics in head and neck squamous cell carcinoma (HNSCC). The MAPK kinase (MEK) inhibitor trametinib has shown efficacy to treat HNSCC; however, the molecular mechanism remains unclear. Methods: HNSCC lines, mouse models, Western blot, and flow cytometry were employed to analyze the anticancer effects of trametinib. Results: The JHU-011, JHU-022, and JHU-029 HNSCC cells with different genetic alterations were highly susceptible to trametinib. Trametinib effectively reduced EGFR expression, which was accompanied by the reduction of pro-survival protein MYC, and the increased expression of a MYC-targeted cyclin-dependent kinase inhibitor p27kip1 and pro-apoptotic protein BIM. Trametinib resulted in G1 arrest of the cells, markedly reduced cell numbers in S phase, and significantly increased apoptosis. In mouse models, trametinib strongly inhibited tumors growth. Conclusions: The MAPK–ERK signaling inhibition by trametinib may target EGFR and the downstream proteins against HNSCC

Salsolinol increases amplitude and decreases paired-pulse ratio (PPR) of evoked EPSCs (eEPSCs) recorded from p-VTA DA neurons.

<p>eEPSCs were recorded in the presence of bicuculline (10 µM) at a holding potential of −70 mV. A, Salsolinol (0.1 µM) sharply increased the peak amplitude of eEPSC₁ and had minimal effect on that of eEPSC₂ evoked by paired stimulation (at 50- ms interval) within the VTA, and hence reduced the PPR (EPSC₂/EPSC₁). B, Time course of salsolinol-induced enhancement of eEPSC₁ amplitude in one experiment. C, Summary of salsolinol-induced changes (%) in eEPSC₁ amplitude and PPR (Mean ± SEM, from eleven neurons). *P<0.05, **P<0.01, paired t-test for salsolinol vs. pre-salsolinol control.</p

Salsolinol-induced stimulation of dopaminergic (DA) neurons is attenuated by APV and DNQX.

<p>A1, Traces illustrate spike discharge at the times indicated in A2. A2, Time course of the increase in the ongoing pacemaking firing rate, recorded from a current-clamped DA neuron in the posterior ventral tegmental area (p-VTA) of a rat, by 0.1 µM salsolinol. B1, Traces obtained at the times indicated in B2. B2, Time course of the effect of salsolinol on the firing rate of a DA neuron in the presence of APV (50 µM) and DNQX (20 µM), the antagonists of NMDA and AMPA receptors. C, Summary plot of decease in firing rate by APV + DNQX. D, Summary plot (means ± S.E.M.) of increase in firing rate of p-VTA DA neurons induced by salsolinol (0.1 µM) in ACSF is larger than that in the APV+DNQX. Numbers in bars indicate numbers of neurons tested. *P<0.05, **P<0.01, paired t-test for salsolinol vs. pre-salsolinol control. Unpaired t-test for salsolinol vs. APV+DNQX+salsolinol.</p

SKF83566 attenuates salsolinol-induced excitation of p-VTA DA neurons.

<p>A, Ongoing firing in the presence of SKF83566 (10 µM), recorded from a current-clamped p-VTA DA neuron, was increased by salsolinol (0.1 µM). B, Pooled data show that in the presence of SKF83566, salsolinol induced an increase in firing rate of p-VTA DA neurons from thirteen cells. C, Summary (means ± S.E.M.) of the effects of salsolinol (0.1 µM) on DA neuron firing rate in the absence (ACSF) and presence of SKF 83566 (SKF 63566). Numbers of cells are indicated in the brackets. *P<0.05 by un-paired t-test, salsolinol vs. SKF 83566+salsolinol.</p