Comparative Study of Antibacterial Properties of Emodin and Enrofloxacin Against Aeromonas hydrophila

Antibacterial properties of emodin, extracted from rhubarb, and enrofloxacin, against Aeromonas hydrophila, were assessed in this study. The minimum inhibitory concentration (MIC) values of emodin and enrofloxacin to fight A. hydrophila WJ2011BJ44 were found to be 100ug/ml and 9.375ug/ml, respectively. To understand the mechanisms of action of emodin and enrofloxcain against A. hydrophila we studied antibacterial activity, bacterial membrane permeability, and ultrastructure of A. hydrophila cells treated with emodin, enrofloxacin individually, and the combination of both. The results shown in the growth curve of A. hydrophila treated with different concentrations (from 0 MIC to 4 MIC) of emodin and enrofloxacin were similar and stable, and there was no significant difference in the growth curve of different treatment groups. There were significant differences in the K+ concentration among all treatment groups from 1 h to 8 h after incubation compared with the control. The highest K+ concentration was observed in the emodin+enrofloxacin group from 1 h to 8 h after incubation. PI fluorescence signal of untreated A. hydrophila cells and A. hydrophila cells treated with emodin, or enrofloxacin individually, or the combination of both were 0.89, 11.4, 13.98 and 18.3, respectively. The mortality of A. hydrophila cells treated with the combination of emodin and enrofloxacin was greatest compared with other groups. These results indicated that 2 MIC emodin, 2 MIC enroflxacin, and combination of 1 MIC emodin and 1 MIC enrofloxacin can inhibit the growth of A. hydrophila, increase bacterial membrane permeability, and damage cell membrane integrity. The combination of 1 MIC concentration emodin and 1 MIC concentration enrofloxacin produced the best antibacterial activity against A. hydrophila

Effects of Dietary Protein Level on Growth Performance, Muscle Composition, Blood Composition, and Digestive Enzyme Activity of Wuchang Bream (Megalobrama amblycephala) Fry

The purpose of this study was to determine the dietary protein requirement and effects of dietary protein level on growth performance, muscle composition, blood composition, and digestive enzyme activity in Wuchang bream fry. Five isoenergetic and isolipidic semi-purified diets were formulated to contain 28%, 30%, 32%, 34%, or 36% (dry matter) dietary protein. Diets were fed to triplicate groups of 25 fishes (16.08±0.03 g) to near satiation three times a day in a closed recirculation system for 10 weeks. Weight gain, specific growth rate, and feed conversion ratio significantly improved as the dietary protein content increased up to 34%. The protein efficiency ratio, hepatosomatic index, and viscerosomatic index significantly dropped as the dietary protein rose while the Fulton condition factor was positively correlated to the dietary protein level. Increased dietary protein resulted in increased muscle protein content and decreased lipid content. Red blood cell, hemoglobin, and hematocrit counts increased significantly with the increase in dietary protein. Serum triiodothyronine and thyroxine significantly rose as the dietary protein rose but serum aspartate aminotransferase significantly dropped. Intestinal protease and amylase activity rose significantly with the increase in dietary protein while lipase tended to drop. On the basis of broken-line regression analysis of weight gain and FCR, the dietary protein requirement of Wuchang bream fry is 32-33%

MEDALT: Single-cell copy number lineage tracing enabling gene discovery

We present a Minimal Event Distance Aneuploidy Lineage Tree (MEDALT) algorithm that infers the evolution history of a cell population based on single-cell copy number (SCCN) profiles, and a statistical routine named lineage speciation analysis (LSA), whichty facilitates discovery of fitness-associated alterations and genes from SCCN lineage trees. MEDALT appears more accurate than phylogenetics approaches in reconstructing copy number lineage. From data from 20 triple-negative breast cancer patients, our approaches effectively prioritize genes that are essential for breast cancer cell fitness and predict patient survival, including those implicating convergent evolution.The source code of our study is available at https://github.com/KChen-lab/MEDALT

Role of LKB1-CRTC1 on Glycosylated COX-2 and Response to COX-2 Inhibition in Lung Cancer

Cyclooxygenase-2 (COX-2) directs the synthesis of prostaglandins including PGE-2 linking inflammation with mitogenic signaling. COX-2 is also an anticancer target, however, treatment strategies have been limited by unreliable expression assays and by inconsistent tumor responses to COX-2 inhibition

Synphilin-1 Enhances α-Synuclein Aggregation in Yeast and Contributes to Cellular Stress and Cell Death in a Sir2-Dependent Manner

© 2010 Büttner et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Parkinson’s disease is characterized by the presence of cytoplasmic inclusions, known as Lewy bodies, containing both aggregated α-synuclein and its interaction partner, synphilin-1. While synphilin-1 is known to accelerate inclusion formation by α-synuclein in mammalian cells, its effect on cytotoxicity remains elusive. Methodology/Principal Findings: We expressed wild-type synphilin-1 or its R621C mutant either alone or in combination with α-synuclein in the yeast Saccharomyces cerevisiae and monitored the intracellular localization and inclusion formation of the proteins as well as the repercussions on growth, oxidative stress and cell death. We found that wild-type and mutant synphilin-1 formed inclusions and accelerated inclusion formation by α-synuclein in yeast cells, the latter being correlated to enhanced phosphorylation of serine-129. Synphilin-1 inclusions co-localized with lipid droplets and endomembranes. Consistently, we found that wild-type and mutant synphilin-1 interacts with detergent-resistant membrane domains, known as lipid rafts. The expression of synphilin-1 did not incite a marked growth defect in exponential cultures, which is likely due to the formation of aggresomes and the retrograde transport of inclusions from the daughter cells back to the mother cells. However, when the cultures approached stationary phase and during subsequent ageing of the yeast cells, both wild-type and mutant synphilin-1 reduced survival and triggered apoptotic and necrotic cell death, albeit to a different extent. Most interestingly, synphilin-1 did not trigger cytotoxicity in ageing cells lacking the sirtuin Sir2. This indicates that the expression of synphilin-1 in wild-type cells causes the deregulation of Sir2-dependent processes, such as the maintenance of the autophagic flux in response to nutrient starvation. Conclusions/Significance: Our findings demonstrate that wild-type and mutant synphilin-1 are lipid raft interacting proteins that form inclusions and accelerate inclusion formation of α-synuclein when expressed in yeast. Synphilin-1 thereby induces cytotoxicity, an effect most pronounced for the wild-type protein and mediated via Sir2-dependent processes.This work was supported by grants from IWT-Vlaanderen (SBO NEURO-TARGET), the K.U.Leuven Research Fund (K.U.Leuven BOF-IOF) and K.U.Leuven R&D to JW, a Tournesol grant from Egide (Partenariat Hubert Curien) in France in collaboration with the Flemish Ministry of Education and the Fund of Scientific Research of Flanders (FWO) in Belgium to JW, MCG and LB, a shared PhD fellowship of the EU-Marie Curie PhD Graduate School NEURAD to JW, MCG and LB, grants of the Austrian Science Fund FWF (Austria) to FM and DR (S-9304-B05), to FM and SB (LIPOTOX), and to SB (T-414-B09; Hertha-Firnberg Fellowship) and an EMBO Installation Grant, a Marie Curie IRG, and a grant of the Fundação para a Ciência e Tecnologia (PTDC/SAU-NEU/105215/2008) to TFO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Using State Space Exploration to Determine How Gene Regulatory Networks Constrain Mutation Order in Cancer Evolution

Cancer develops via the progressive accumulation of somatic mutations, which subvert the normal operation of the gene regulatory network of the cell. However, little is known about the order in which mutations are acquired in successful clones. A particular sequence of mutations may confer an early selective advantage to a clone by increasing survival or proliferation, or lead to negative selection by triggering cell death. The space of allowed sequences of mutations is therefore constrained by the gene regulatory network. Here, we introduce a methodology for the systematic exploration of the effect of every possible sequence of oncogenic mutations in a cancer cell modelled as a qualitative network. Our method uses attractor identification using binary decision diagrams and can be applied to both synchronous and asynchronous systems. We demonstrate our method using a recently developed model of ER-negative breast cancer. We show that there are differing levels of constraint in the order of mutations for different combinations of oncogenes, and that the effects of ErbB2/HER2 over-expression depend on the preceding mutations

Fasted and postprandial response of serum physiological response, hepatic antioxidant abilities and HSP70 expression in Wuchang bream (Megalobrama amblycephala) fed different dietary carbohydrate levels

The effect of dietary carbohydrate (CHO) level on serum physiological response, hepatic antioxidant abilities and heat shock protein 70 (HSP70) expression of Wuchang bream (Megalobrama amblycephala) was studied. Two isonitrogenous (28.56% crude protein) and isolipidic (5.28% crude lipid) diets were formulated to contain 30% or 53% wheat starch. Diets were fed for 90 days to fish in triplicate tanks (28 fish per tank). At the end of feeding trial, significantly higher serum triglyceride level, insulin level, cortisol level, and malondialdehyde (MDA) content were observed in fish fed the 53% CHO diet, while significantly lower serum total protein content, alkaline phosphatase activity, superoxide dismutase activity and total antioxidative capacity were found in fish fed the 53% CHO diet compared with those fed the 30% diet. The relative level of hepatic heat shock protein 70 mRNA was significantly higher in the 53% CHO group than that in the 30% CHO at 6, 12 and 48 h after feeding. Ingestion of 53% dietary CHO impacts the nonspecific immune ability and causes metabolic stress in Megalobrama amblycephala

Effect of High Dietary Carbohydrate on the Growth Performance, Blood Chemistry, Hepatic Enzyme Activities and Growth Hormone Gene Expression of Wuchang Bream () at Two Temperatures

The effects of high carbohydrate diet on growth, serum physiological response, and hepatic heat shock protein 70 expression in Wuchang bream were determined at 25°C and 30°C. At each temperature, the fish fed the control diet (31% CHO) had significantly higher weight gain, specific growth rate, protein efficiency ratio and hepatic glucose-6-phosphatase activities, lower feed conversion ratio and hepatosomatic index (HSI), whole crude lipid, serum glucose, hepatic glucokinase (GK) activity than those fed the high-carbohydrate diet (47% CHO) (p<0.05). The fish reared at 25°C had significantly higher whole body crude protein and ash, serum cholesterol and triglyceride, hepatic G-6-Pase activity, lower glycogen content and relative levels of hepatic growth hormone (GH) gene expression than those reared at 30°C (p<0.05). Significant interaction between temperature and diet was found for HSI, condition factor, hepatic GK activity and the relative levels of hepatic GH gene expression (p<0.05)

The effects of a government\u27s subsidy program: accessibility beyond affordability

Rural consumers may face not only the challenge of affordability but also the problem of limited accessibility. Can a government&rsquo;s subsidy program effectively address these issues? This paper examines the impact of a large-scale subsidy program, &ldquo;Household electrical appliances going to the countryside,&rdquo; offered by the Chinese government. The government regulation imposes a price subsidy combined with a price ceiling on products in the program. We consider two effects of the subsidy: the retail price is lowered to make the product more affordable to consumers, and manufacturers are encouraged to expand their distribution coverage to make products more accessible to consumers. We build a dynamic model of oligopoly to study how firms adjust their distribution coverage. Conditional on the model estimates, we evaluate the program&rsquo;s effects on social welfare, consumer surplus, and firms&rsquo; market performance and marketing channel decisions through counterfactual analyses. We find that the subsidy program increases social welfare by CNY 0.209 billion, as a result of a subsidy expense of CNY 0.236 billion. When breaking down the impact, we find it increases consumer surplus by CNY 0.184 billion (50%), manufacturers&rsquo; profits by CNY 0.125 billion (53%), and manufacturers&rsquo; payoffs by CNY 2.5 million (17%). Specifically, 14% (13.2%) of the consumer surplus (firm profit) increases are from changes in distribution coverage, and the rest is from the subsidy (price changes). The program&rsquo;s return of investment (i.e., social welfare minus subsidy expense), which is negative, however, could be improved by applying a relatively lower subsidy rate. This paper was accepted by Juanjuan Zhang, marketing