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41.
Martha Lissete Morales Villarreal Marina Padilha Antonio Diogo Silva Vieira Bernadette Dora Gombossy de Melo Franco Rafael Chacon Ruiz Martinez Susana Marta Isay Saad 《PloS one》2013,8(12)
Species-specific Quantitative Real Time PCR (qPCR) alone and combined with the use of propidium monoazide (PMA) were used along with the plate count method to evaluate the survival of the probiotic strains Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis Bb-12, and the bacteriocinogenic and potentially probiotic strain Lactobacillus sakei subsp. sakei 2a in synbiotic (F1) and probiotic (F2) petit-suisse cheeses exposed throughout shelf-life to in vitro simulated gastrointestinal tract conditions. The three strains studied showed a reduction in their viability after the 6 h assay. Bb-12 displayed the highest survival capacity, above 72.6 and 74.6% of the initial populations, respectively, by plate count and PMA-qPCR, maintaining population levels in the range or above 6 log CFU/g. The prebiotic mix of inulin and FOS did not offer any additional protection for the strains against the simulated gastrointestinal environment. The microorganisms'' populations were comparable among the three methods at the initial time of the assay, confirming the presence of mainly viable and culturable cells. However, with the intensification of the stress induced throughout the various stages of the in vitro test, the differences among the methods increased. The qPCR was not a reliable enumeration method for the quantification of intact bacterial populations, mixed with large numbers of injured and dead bacteria, as confirmed by the scanning electron microscopy results. Furthermore, bacteria plate counts were much lower (P<0.05) than with the PMA-qPCR method, suggesting the accumulation of stressed or dead microorganisms unable to form colonies. The use of PMA overcame the qPCR inability to differentiate between dead and alive cells. The combination of PMA and species-specific qPCR in this study allowed a quick and unequivocal way of enumeration of viable closely related species incorporated into probiotic and synbiotic petit-suisse cheeses and under stress conditions. 相似文献
42.
Cyril Rauch Stuart W. Paine Peter Littlewood 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Failure of treatment in over 90% of patients with metastatic cancer is due to acquired MDR. P-glycoprotein (Pgp) remains the archetypal drug membrane transporter expressed in many MDR cancer cells. Albeit the ATPase activity of Pgp is triggered by the presence of drug in the membrane, it is commonly assumed that when two drug molecules meet the same Pgp the protein cannot handle them efficiently due to steric effects and as a result the ATPase activity drops. However it is also possible that drug accumulating in the lipid-phase may affect the membrane in such a way that it imposes the mechanical closure of transporters by opposing the force mediated by ATP consumption. In this context, long range interactions between drug and membrane proteins could exist.Methods
Recent data concerning Pgp structure have allowed us to formalize this hypothesis and we present a physico-mathematical model that is not based on predictive QSAR or other empirical methods applied to experimental data.Results
Long range mechanical interactions between Pgp and drugs are predicted to occur at an external concentration of drug ~ 10–100 μM as previously determined experimentally at which concentration ~ 50% of transporters should be rendered inactive.Conclusion
Distance interaction(s) between Pgp and drugs exist explaining an ill-defined effect concerning the ability of any drug to inhibit Pgp once a threshold concentration in the membrane has been reached.General significance
Potential application of the theory in the field of pharmacology concentrating on the notion of molecular promiscuity and toxicity in drug discovery prediction is discussed. 相似文献43.
Molecular cloning,expression, and hormonal regulation of the chicken microsomal triglyceride transfer protein 总被引:1,自引:0,他引:1
N. Erwin Ivessa Edward Rehberg Bernadette Kienzle Fridolin Seif Robert Hermann Marcela Hermann Wolfgang J. Schneider David A. Gordon 《Gene》2013
During an egg-laying cycle, oviparous animals transfer massive amounts of triglycerides, the major lipid component of very low density lipoprotein (VLDL), from the liver to the developing oocytes. A major stimulus for this process is the rise in estrogen associated with the onset of an egg-laying cycle. In mammals, the microsomal triglyceride transfer protein (MTP) is required for VLDL assembly and secretion. To enable studies to determine if MTP plays a role in basal and estrogen-stimulated VLDL assembly and secretion in an oviparous vertebrate, we have cloned and sequenced the chicken MTP cDNA. This cDNA encodes a protein of 893 amino acids with an N-terminal signal sequence. The primary sequence of chicken MTP is, on average, 65% identical to that of mammalian homologs, and 23% identical to the Drosophila melanogaster protein. We have obtained a clone of chicken embryo fibroblast cells that stably express the avian MTP cDNA and show that these cells display MTP activity as measured by the transfer of a fluorescently labeled neutral lipid. As in mammals, chicken MTP is localized to the endoplasmic reticulum as revealed by indirect immunofluorescence and by the fact that its N-linked oligosaccharide moiety remains sensitive to endoglycosidase H. Endogenous, enzymatically active MTP is also expressed in an estrogen receptor-expressing chicken hepatoma cell line that secretes apolipoprotein B-containing lipoproteins. In this cell line and in vivo, the expression and activity of MTP are not influenced by estrogen. Therefore, up-regulation of MTP in the liver is not required for the increased VLDL assembly during egg production in the chicken. This indicates that MTP is not rate-limiting, even for the massive estrogen-induced secretion of VLDL accompanying an egg-laying cycle. 相似文献
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45.
Christine Rauch Michael Trieb Fajar R. Wibowo Bernd Wellenzohn Erwin Mayer Klaus R. Liedl 《Journal of biomolecular structure & dynamics》2013,31(6):695-706
Abstract CpG methylation determines a variety of biological functions of DNA. The methylation signal is interpreted by proteins containing a methyl-CpG binding domain (MBDs). Based on the NMR structure of MBD1 complexed with methylated DNA we analysed the recognition mode by means of molecular dynamics simulations. As the protein is monomeric and recognizes a symmetrically methylated CpG step, the recognition mode is an asymmetric one. We find that the two methyl groups do not contribute equally to the binding energy. One methyl group is associated with the major part of the binding energy and the other one nearly does not contribute at all. The contribution of the two cytosine methyl groups to binding energy is calculated to be ?3.6 kcal/mol. This implies a contribution of greater than two orders of magnitude to the binding constant. The conserved amino acid Asp32 is known to be essential for DNA binding by MBD1, but so far no direct contact with DNA has been observed. We detected a direct DNA base contact to Asp32. This could be the main reason for the importance of this amino acid. MBD contacts DNA exclusively in the major groove, the minor groove is reserved for histone contacts. We found a deformation of the minor groove shape due to complexation by MBD1, which indicates an information transfer between the major and the minor groove. 相似文献
46.
Dr. Anne Pisarski Christine Brook Philip Bohle Cynthia Gallois Bernadette Watson Sarah Winch 《Chronobiology international》2013,30(6):1363-1377
The present study contributes to theory and practice through the development of a model of shift‐work tolerance with the potential to indicate interventions that reduce nurses' intention toward turnover and increase job satisfaction in hospital‐based settings. Survey data from 1257 nurses were used to conduct structural equation modeling that examine the direct and indirect effects of supervisor and colleague support, team identity, team climate, and control over working environment on time‐based work/life conflict, psychological well‐being, physical symptoms, job satisfaction, and turnover intention. The analysis of the proposed model revealed a good fit The chi‐square difference test was non‐significant (χ2(26)=338.56), the fit indices were high (CFI=.923, NFI=.918, and NNFI=.868), the distribution of residuals was symmetric and approached zero, the average standardized residual was low (AASR=.04), and the standardized RMR was. 072. In terms of the predictor variable, the final model explained 48% of the variance in turnover intention. The data revealed considerable evidence of both direct effects on adjustment and complex indirect links between levels of adjustment and work‐related social support, team identity, team climate, and control. Nurses with high supervisor and coworker support experienced more positive team climates, identified more strongly with their team, and increased their perceptions of control over their work environment. This in turn lowered their appraisals of their time‐based work/life conflict, which consequently increased their psychological well‐being and job satisfaction and reduced their physical health symptoms and turnover intention. The type of shift schedule worked by the nurses influenced levels of turnover intention, control over work environment, time‐based work/life conflict, and physical symptoms. 相似文献
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48.
Joanna Szkandera Gudrun Absenger Bernadette Liegl-Atzwanger Martin Pichler Michael Stotz Stefan Gerger Maximilian Zacherl Wilfried Renner Miao Haijun Andreas Leithner Armin Gerger 《Cancer epidemiology》2013,37(6):1003-1009
BackgroundDNA repair mechanisms play a major role in cancer risk and progression. Germline variants in DNA repair genes may result in altered gene function and/or activity, thereby causing inter-individual differences in a patient's tumor recurrence capacity. In genes of the DNA repair pathway the gene variants RAD51 rs1801320 G > C, XRCC2 rs3218536 G > A and XPD rs13181 A > C have been previously related to genetic predisposition and prognosis of various cancer entities. In this study we investigated the association between these polymorphisms and time to recurrence (TTR) and overall survival (OS) in soft-tissue sarcoma (STS) patients after curative surgery.MethodsTwo hundred sixty STS patients were included in this retrospective study. Germline DNA was genotyped by 5′-exonuclease (TaqMan) technology. Kaplan Meier curves and multivariate Cox proportional models were calculated for TTR and OS.ResultsA statistically significant association was observed between tumor grade and adjuvant radiotherapy and TTR and between tumor grade and OS. No association was found between RAD51 rs1801320 G > C, XRCC2 rs3218536 G > A and XPD rs13181 A > C and TTR and OS in univariate and multivariate analysis.ConclusionOur results underline a prognostic effect of tumor grade and adjuvant radiotherapy in STS patients but indicate no association between RAD51 rs1801320 G > C, XRCC2 rs3218536 G > A and XPD rs13181 A > C and clinical outcome in STS patients after curative surgery. 相似文献
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Nataliya Di Donato Ying Y. Jean A. Murat Maga Briana D. Krewson Alison B. Shupp Maria I. Avrutsky Achira Roy Sarah Collins Carissa Olds Rebecca A. Willert Agnieszka M. Czaja Rachel Johnson Jessi A. Stover Steven Gottlieb Deborah Bartholdi Anita Rauch Amy Goldstein Victoria Boyd-Kyle Kimberly A. Aldinger Ghayda M. Mirzaa Anke Nissen Karlla W. Brigatti Erik G. Puffenberger Kathleen J. Millen Kevin A. Strauss William B. Dobyns Carol M. Troy Robert N. Jinks 《American journal of human genetics》2016,99(5):1117-1129