Identifying essential genes in bacteria supports to identify potential drug targets and an understanding of minimal requirements
for a synthetic cell. However, experimentally assaying the essentiality of their coding genes is resource intensive and not
feasible for all bacterial organisms, in particular if they are infective. 相似文献
Extracting biomedical information from large metabolomic datasets by multivariate data analysis is of considerable complexity. Common challenges include among others screening for differentially produced metabolites, estimation of fold changes, and sample classification. Prior to these analysis steps, it is important to minimize contributions from unwanted biases and experimental variance. This is the goal of data preprocessing. In this work, different data normalization methods were compared systematically employing two different datasets generated by means of nuclear magnetic resonance (NMR) spectroscopy. To this end, two different types of normalization methods were used, one aiming to remove unwanted sample-to-sample variation while the other adjusts the variance of the different metabolites by variable scaling and variance stabilization methods. The impact of all methods tested on sample classification was evaluated on urinary NMR fingerprints obtained from healthy volunteers and patients suffering from autosomal polycystic kidney disease (ADPKD). Performance in terms of screening for differentially produced metabolites was investigated on a dataset following a Latin-square design, where varied amounts of 8 different metabolites were spiked into a human urine matrix while keeping the total spike-in amount constant. In addition, specific tests were conducted to systematically investigate the influence of the different preprocessing methods on the structure of the analyzed data. In conclusion, preprocessing methods originally developed for DNA microarray analysis, in particular, Quantile and Cubic-Spline Normalization, performed best in reducing bias, accurately detecting fold changes, and classifying samples.
It has been reported that Toll-like receptor 4 (TLR4) deficiency reduces infarct size after myocardial ischemia/reperfusion
(MI/R). However, measurement of MI/R injury was limited and did not include cardiac function. In a chronic closed-chest model we assessed whether cardiac function is preserved in TLR4-deficient mice (C3H/HeJ) following MI/R, and whether myocardial and systemic cytokine expression differed
compared to wild type (WT). 相似文献
Studies on the subcellular distribution of rat liver nucleotide pyrophosphatase activity revealed its presence in the plasma membrane and the endoplasmic reticulum only. The enzymes from either source were solubilized specifically with trypsin without an apparent change of their catalytic properties. A 200-fold and 1600-fold purification, respectively, was achieved by a procedure including DEAE-cellulose and affinity-chromatography with AMP as ligand, gel filtration on Sephadex G-200 and gel electrophoresis. Both nucleotide pyrophosphatases were isolated as electrophoretically homogeneous soluble proteins. They were shown to contain carbohydrate moieties. The electrophoretic mobility of both enzymes in polyacrylamide gels was identical at three pH values. Dodecylsulfate gel electrophoresis indicated a molecular weight of 137 000 for both glycoproteins. The enzymes hydrolyze a variety of purine and pyrimidine nucleotides yielding a 5'-nucleoside monophosphate. Adenosine 3':5'-monophosphate, nucleic acids and phosphate monoesters are not cleaved, but p-nitrophenyl-thymidine5'-monophosphate is readily hydrolyzed. In view of their substrate and inhibitor specificities the enzymes are considered nucleotide pyrophosphatases rather than phosphodiesterases. 相似文献
Abstract: The molecular origin of protein stability has been the subject of active research for more than a generation (R. Jaenicke (1991) Eur. J. Biochem. 202, 715–728). Faced with the discovery of extremophiles, in recent years the problem has gained momentum, especially because of its biotechnological potential. In analyzing a number of enzymes from the hyperthermophilic bacterium Thermotoga maritima , it has become clear that the excess free energy of stabilization is equivalent to only a few weak bonds ( ΔΔG stab≈ 50 kJ/mol). As taken from the comparison of homologous enzymes from mesophiles, thermophiles and hyperthermophiles, these accumulate from local interactions (especially ion pairs), enhanced secondary or supersecondary structure, and improved packing of domains and/or subunits, without significantly altering the overall topology. In this review, glyceraldehyde-3-phosphate dehydrogenase will be discussed as a representative example to illustrate possible adaptive strategies to the extreme thermal stress in hydrothermal vents. 相似文献
Adriamycin and mitomycin C were previously found to modulate the sensitivity of lymphoma cells to lysis by certain effectors of immunity and this modulation was dependent on drug concentration. In the present studies, RDM4 lymphoma cells were treated with different concentrations of the two drugs for 24 h in culture. These treatments resulted in changes in the lipid composition, membrane fluidity, cell size distribution, and permeability to 51CrO4, Trypan blue, Acridine orange and trimethylaminodiphenylhexatriene (TMA-DPH) of the cells. Changes in some of these parameters, as a function of drug concentration, resulted in dose-response curves which were bell-like shaped, hence paradoxical similarities between non-drug-treated cells and cells treated with higher drug concentrations were observed. 相似文献
Summary Electron microscopic studies of peripheral nerves and spinal cord white matter of adult mice, as prepared by the freeze-etching method, show distinct differences in the periodicity of the myelin lamellae as well as of the ultrastructural lamellar pattern. A periodicity of 185 Å is to be determined for peripheral myelin whereas it is 160 Å in the myelin of central origin.In contrast to the appearance in the peripheral myelin the lamellar structure in the central myelin sheath is less pronounced and tends towards a fundamental repeating unit of 80 Å.This work was supported by the Swiss National Foundation (Nr. 4065). 相似文献
Summary Penicillin G was extracted from a model medium with a secondary amine (Amberlite LA-2) as carrier in n-butylacetate as solvent in a 7.6 m high pilot plant Karr-column at different stroke frequencies, throughput of the phases, concentrations of Penicillin G and carrier and ratios of the throughputs of the aqueous and organic phases. Up to penicillin concentrations of 30 gl–1, throughputs of the aqueous phase of 100 lh–1 and throughput ratios of the aqueous phase-to-organic phase of 3, very high degrees of extraction (99%) can be achieved with a penicillin loss below 1%.Symbols a
specific interfacial area with regard to the volume of the continuous phase
- C
partition coefficient
- cA, cA, i
concentration of carrier (sec. amine) in the bulk at the interface
- cAHP, cAHP, i
concentration of complex in the bulk at the interface
- cH
proton concentration
- cHPa, cHPa,i
concentration of free acid in the bulk of the aqueous phase at the interface
- cHPo, cHPo, i
concentration of free acid in the bulk of the organic phase, at the interface
- cP, cP, i
concentration of acid anions in the bulk of the aqueous phase, at the interface
- d32
Sauter droplet diameter
- E
degree of extraction
- f
stroke frequency
- KG
reaction equilibrium constant
- Kphys
distribution coefficient
- N
number of stages in cascade
- t
mean residence time of the aqueous phase
-
aq
throughput of the aqueous phase
-
o
throughput of the organic phase
- Z
dimensionless longitudinal coordinate of the column with regard to its active length (4 m)
-
holdup of the organic phase 相似文献