Heat Treated NiP–SiC Composite Coatings: Elaboration and Tribocorrosion Behaviour in NaCl Solution

Tribocorrosion behaviour of heat-treated NiP and NiP–SiC composite coatings was investigated in a 0.6 M NaCl solution. The tribocorrosion tests were performed in a linear sliding tribometer with an electrochemical cell interface. It was analyzed the influence of SiC particles dispersion in the NiP matrix on current density developed, on coefficient of friction and on wear volume loss. The results showed that NiP–SiC composite coatings had a lower wear volume loss compared to NiP coatings. However, the incorporation of SiC particles into the metallic matrix affects the current density developed by the system during the tribocorrosion test. It was verified that not only the volume of co-deposited particles (SiC vol.%) but also the number of SiC particles per coating area unit (and consequently the SiC particles size) have made influence on the tribocorrosion behaviour of NiP–SiC composite coatings

Fast- or Slow-inactivated State Preference of Na+ Channel Inhibitors: A Simulation and Experimental Study

Sodium channels are one of the most intensively studied drug targets. Sodium channel inhibitors (e.g., local anesthetics, anticonvulsants, antiarrhythmics and analgesics) exert their effect by stabilizing an inactivated conformation of the channels. Besides the fast-inactivated conformation, sodium channels have several distinct slow-inactivated conformational states. Stabilization of a slow-inactivated state has been proposed to be advantageous for certain therapeutic applications. Special voltage protocols are used to evoke slow inactivation of sodium channels. It is assumed that efficacy of a drug in these protocols indicates slow-inactivated state preference. We tested this assumption in simulations using four prototypical drug inhibitory mechanisms (fast or slow-inactivated state preference, with either fast or slow binding kinetics) and a kinetic model for sodium channels. Unexpectedly, we found that efficacy in these protocols (e.g., a shift of the “steady-state slow inactivation curve”), was not a reliable indicator of slow-inactivated state preference. Slowly associating fast-inactivated state-preferring drugs were indistinguishable from slow-inactivated state-preferring drugs. On the other hand, fast- and slow-inactivated state-preferring drugs tended to preferentially affect onset and recovery, respectively. The robustness of these observations was verified: i) by performing a Monte Carlo study on the effects of randomly modifying model parameters, ii) by testing the same drugs in a fundamentally different model and iii) by an analysis of the effect of systematically changing drug-specific parameters. In patch clamp electrophysiology experiments we tested five sodium channel inhibitor drugs on native sodium channels of cultured hippocampal neurons. For lidocaine, phenytoin and carbamazepine our data indicate a preference for the fast-inactivated state, while the results for fluoxetine and desipramine are inconclusive. We suggest that conclusions based on voltage protocols that are used to detect slow-inactivated state preference are unreliable and should be re-evaluated

Neurospora from natural populations: Population genomics insights into the Life history of a model microbial Eukaryote

The ascomycete filamentous fungus Neurospora crassa played a historic role in experimental biology and became a model system for genetic research. Stimulated by a systematic effort to collect wild strains initiated by Stanford geneticist David Perkins, the genus Neurospora has also become a basic model for the study of evolutionary processes, speciation, and population biology. In this chapter, we will first trace the history that brought Neurospora into the era of population genomics. We will then cover the major contributions of population genomic investigations using Neurospora to our understanding of microbial biogeography and speciation, and review recent work using population genomics and genome-wide association mapping that illustrates the unique potential of Neurospora as a model for identifying the genetic basis of (potentially adaptive) phenotypes in filamentous fungi. The advent of population genomics has contributed to firmly establish Neurospora as a complete model system and we hope our review will entice biologists to include Neurospora in their research

Protective Effect of Hainosankyuto, a Traditional Japanese Medicine, on Streptococcus pyogenes Infection in Murine Model

BACKGROUND: Streptococcus pyogenes (S. pyogenes) causes various serious diseases including necrotizing fasciitis and streptococcal toxic shock syndrome. One serious problem observed recently with S. pyogenes therapy is attenuation of the antibiotic effect, especially penicillin treatment failure and macrolide resistance. Hainosankyuto, a traditional Japanese medicine based on ancient Chinese medicine, has been used for treatment of infectious purulent diseases in Japan. In this study, we investigated the protective and therapeutic efficacy of Hainosankyuto against S. pyogenes-skin infection. METHODOLOGY/PRINCIPAL FINDINGS: A broth microdilution method revealed that Hainosankyuto did not show a direct anti-bacterial effect against S. pyogenes. Force-feeding Hainosankyuto to infected mice for 4 consecutive days increased the survival rate and reduced the size of local skin lesions compared with mice fed PBS. Although we did not find the significant recovery of survival rate in Hainosankyuto administration only after S. pyogenes infection, the sizes of ulcer lesion were significant smaller after Hainosankyuto administration compared with mice fed PBS. No difference was observed in the anti-bacterial effect of Hainosankyuto between macrolide-susceptible and -resistant strains. Blood bactericidal assay showed that the survival rate of S. pyogenes using the blood from Hainosankyuto-treated mice was lower than that using the blood from untreated mice. We also found increased levels of IL-12, IFN-γ and a decreased level of TNF-α in the serum of S. pyogenes-infected mice treated with Hainosankyuto. Mouse peritoneal macrophage from Hainosankyuto-treated mice had significant phagocytic activity and increased mRNA levels of IL-12, IFN-γ and decreased mRNA level of TNF-α compared with control macrophage. CONCLUSIONS/SIGNIFICANCE: Hainosankyuto increased survival rate after S. pyogenes infection and up-regulated both blood bactericidal activity and macrophage phagocytic activity through modulation of inflammatory cytokines. Our data also suggest Hainosankyuto may be useful for the treatment of S. pyogenes infection more prophylactically than therapeutically

Polymorphisms in the Estrogen Receptor 1 and Vitamin C and Matrix Metalloproteinase Gene Families Are Associated with Susceptibility to Lymphoma

BACKGROUND: Non-Hodgkin lymphoma (NHL) is the fifth most common cancer in the U.S. and few causes have been identified. Genetic association studies may help identify environmental risk factors and enhance our understanding of disease mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: 768 coding and haplotype tagging SNPs in 146 genes were examined using Illumina GoldenGate technology in a large population-based case-control study of NHL in the San Francisco Bay Area (1,292 cases 1,375 controls are included here). Statistical analyses were restricted to HIV- participants of white non-Hispanic origin. Genes involved in steroidogenesis, immune function, cell signaling, sunlight exposure, xenobiotic metabolism/oxidative stress, energy balance, and uptake and metabolism of cholesterol, folate and vitamin C were investigated. Sixteen SNPs in eight pathways and nine haplotypes were associated with NHL after correction for multiple testing at the adjusted q<0.10 level. Eight SNPs were tested in an independent case-control study of lymphoma in Germany (494 NHL cases and 494 matched controls). Novel associations with common variants in estrogen receptor 1 (ESR1) and in the vitamin C receptor and matrix metalloproteinase gene families were observed. Four ESR1 SNPs were associated with follicular lymphoma (FL) in the U.S. study, with rs3020314 remaining associated with reduced risk of FL after multiple testing adjustments [odds ratio (OR) = 0.42, 95% confidence interval (CI) = 0.23-0.77) and replication in the German study (OR = 0.24, 95% CI = 0.06-0.94). Several SNPs and haplotypes in the matrix metalloproteinase-3 (MMP3) and MMP9 genes and in the vitamin C receptor genes, solute carrier family 23 member 1 (SLC23A1) and SLC23A2, showed associations with NHL risk. CONCLUSIONS/SIGNIFICANCE: Our findings suggest a role for estrogen, vitamin C and matrix metalloproteinases in the pathogenesis of NHL that will require further validation

Development of a Surface Plasmon Resonance Biosensor for Real-Time Detection of Osteogenic Differentiation in Live Mesenchymal Stem Cells

Surface plasmon resonance (SPR) biosensors have been recognized as a useful tool and widely used for real-time dynamic analysis of molecular binding affinity because of its high sensitivity to the change of the refractive index of tested objects. The conventional methods in molecular biology to evaluate cell differentiation require cell lysis or fixation, which make investigation in live cells difficult. In addition, a certain amount of cells are needed in order to obtain adequate protein or messenger ribonucleic acid for various assays. To overcome this limitation, we developed a unique SPR-based biosensing apparatus for real-time detection of cell differentiation in live cells according to the differences of optical properties of the cell surface caused by specific antigen-antibody binding. In this study, we reported the application of this SPR-based system to evaluate the osteogenic differentiation of mesenchymal stem cells (MSCs). OB-cadherin expression, which is up-regulated during osteogenic differentiation, was targeted under our SPR system by conjugating antibodies against OB-cadherin on the surface of the object. A linear relationship between the duration of osteogenic induction and the difference in refractive angle shift with very high correlation coefficient was observed. To sum up, the SPR system and the protocol reported in this study can rapidly and accurately define osteogenic maturation of MSCs in a live cell and label-free manner with no need of cell breakage. This SPR biosensor will facilitate future advances in a vast array of fields in biomedical research and medical diagnosis

Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines

The study aimed to assess the effects of polyphenols when used in combination with doxorubicin and etoposide, and to determine whether polyphenols sensitised leukaemia cells, causing inhibition of cell proliferation, cell cycle arrest and induction of apoptosis. This study is based on findings in solid cancer tumours, which have shown that polyphenols can sensitize cells to chemotherapy, and induce apoptosis and/or cell-cycle arrest. This could enable a reduction of chemotherapy dose and off-target effects, whilst maintaining treatment efficacy. Quercetin, apigenin, emodin, rhein and cis-stilbene were investigated alone and in combination with etoposide and doxorubicin in two lymphoid and two myeloid leukaemia cells lines. Measurements were made of ATP levels (using CellTiter-Glo assay) as an indication of total cell number, cell cycle progression (using propidium iodide staining and flow cytometry) and apoptosis (NucView caspase 3 assay and Hoechst 33342/propidium iodide staining). Effects of combination treatments on caspases 3, 8 and 9 activity were determined using Glo luminescent assays, glutathione levels were measured using the GSH-Glo Glutathione Assay and DNA damage determined by anti-γH2AX staining. Doxorubicin and etoposide in combination with polyphenols synergistically reduced ATP levels, induced apoptosis and increased S and/or G2/M phase cell cycle arrest in lymphoid leukaemia cell lines. However, in the myeloid cell lines the effects of the combination treatments varied; doxorubicin had a synergistic or additive effect when combined with quercetin, apigenin, emodin, and cis-stilbene, but had an antagonistic effect when combined with rhein. Combination treatment caused a synergistic downregulation of glutathione levels and increased DNA damage, driving apoptosis via caspase 8 and 9 activation. However, in myeloid cells where antagonistic effects were observed, this was associated with increased glutathione levels and a reduction in DNA damage and apoptosis. This study has demonstrated that doxorubicin and etoposide activity were enhanced by polyphenols in lymphoid leukaemia cells, however, differential responses were seen in myeloid cells with antagonistic responses seen in some combination therapies

Comparing factors affecting commencement and cessation of betel quid chewing behavior in Taiwanese adults

<p>Abstract</p> <p>Background</p> <p>Betel quid is the fourth most common used substance in the world after tobacco, alcohol and caffeine. Although factors related to betel quid chewing or cessation of behaviors were reported previously, few studies simultaneously compared both behaviors in the same population. In addition, it is essential to consider time-to-event concept, since the chance of developing or stopping habit may vary over time. The purpose of this study was to compare the risk factors for commencement and cessation of betel quid chewing behaviors in a time-to-event setting.</p> <p>Methods</p> <p>A stratified multi-stage cluster sampling with selection probabilities proportional to size (PPS) was designed for Taiwanese adults with aged 18 years old and above. Kaplan-Meier estimates and Cox proportional hazard regression models were used to compare and calculate the hazard rate ratios for related factors to commencement or cessation of chewing habits.</p> <p>Results</p> <p>In Taiwan, men had a higher betel quid chewing rate (M: 20.9%, W: 1.2%), but woman chewers had a lower cessation rate (M: 27.5%, W: 12.7%). The hazard rate ratio (HRR) of having chewing habit changed from 4.22 (men vs women) univariately to 1.38 multivariablely, which indicated gender differences were confounded by other factors. In multivariable analysis, the risk factors of gender, education and ethnicity were significantly associated with both starting and cessation of betel quid chewing behavior. The factors of occupation, cigarette smoking and alcohol drinking were only associated with starting habit.</p> <p>Conclusion</p> <p>Commencement or cessation of chewing behavior involves a scenario of time, hence it is preferable to use a time-to-event approach for the comparison. The cessation rates of betel quid chewing were decreasingly associated with the daily consumption of betel quid. Hence, reducing of daily amount in betel quid cessation program may be associated with future stopping habit.</p