Gene selection for classification of cancers using probabilistic model building genetic algorithm

Recently, DNA microarray-based gene expression profiles have been used to correlate the clinical behavior of cancers with the differential gene expression levels in cancerous and normal tissues. To this end, after selection of some predictive genes based on signal-to-noise (S2N) ratio, unsupervised learning like clustering and supervised learning like k-nearest neighbor (k NN) classifier are widely used. Instead of S2N ratio, adaptive searches like Probabilistic Model Building Genetic Algorithm (PMBGA) can be applied for selection of a smaller size gene subset that would classify patient samples more accurately. In this paper, we propose a new PMBGA-based method for identification of informative genes from microarray data. By applying our proposed method to classification of three microarray data sets of binary and multi-type tumors, we demonstrate that the gene subsets selected with our technique yield better classification accuracy.     

Age-related changes of elements and relationships among elements in the common bile and pancreatic ducts

To elucidate compositional changes of the common bile and main pancreatic ducts with aging, the authors investigated age-related changes of element contents in the common bile and pancreatic ducts by inductively coupled plasma-atomic emission spectrometry. After ordinary dissection by medical students was finished, the common bile ducts and main pancreatic ducts (pancreatic ducts) were resected and the element contents were determined. The Mg content increased significantly only in the pancreatic duct with aging, but the other element contents did not change significantly in both the common bile and pancreatic ducts with aging. Regarding the relationship among the elements, significant direct correlations were found among the contents of Ca, P, S, and Mg in the common bile ducts, with some exceptions between P and either S or Mg contents. In the pancreatic ducts, significant direct correlations were found between S and Mg contents and between P and Na contents. The relationships in the elements between the common bile and pancreatic ducts were examined. It was found that there were significant direct correlations in the Ca, Mg, and Fe contents between the common bile and pancreatic ducts; that is, as Ca, Mg, and Fe increased in the common bile duct, they increased simultaneously in the pancreatic duct.     

Effects of auditory stimuli correlated with different probabilities of water delivery in a limited-hold temporal schedule

Four rats were exposed to two different tone frequencies, each tone being correlated with independent probabilities of water delivery in a temporally defined schedule. The schedule consisted of a 60-s T cycle, with 30-s t(D) and t(Delta) succesive subcycles. t(D) and t(Delta) were assigned complementary probabilities of water delivery (1.0-0, 0.75-0.25, 0.5-0.5 and 1.0-0) in succesive phases. Each of the first three experimental phases was followed by five consecutive probe sessions using the same probability values, and in which water was delivered independently of responding at the end of each subcycle. Three additional rats were exposed to the same conditions, except that only one tone was used in t(D) and t(Delta). The highest frequencies of responding were observed in two of the rats exposed to differential tone frequencies, an effect that was correlated with lower percentages of lost water deliveries, shorter response latencies, and less variability in the intervals between successive water presentations. In the last phase in which probabilities of water delivery in t(D) and t(Delta) were 1.0 and 0, respectively, response frequency was always higher in t(Delta). These results suggest that the number of water deliveries obtained in the early cycles of every session were responsible for the total number of responses and its correlated effects.     

A new tandem repeat in bovine fibrinogen Aalpha gene

In this study, we describe intraspecies variation in the alphaC connector region of the bovine fibrinogen Aalpha gene. Sequencing and genotyping of six bovine breeds revealed 7 to 10 tandem repeats in the alphaC connector region. In addition, we observed length differences between B. indicus and B. taurus, with the B. indicus having longer fibrinogen alphaC connectors (10-repeat alleles) than B. taurus (7- and 9-repeats). The difference in tandem repeats may be related to the function of blood coagulation system.     

Accumulation of calcium and phosphorus accompanied by inevitable accumulation of magnesium in human arteries

To examine whether there were differences between races in regard to the relationships among element contents in the arteries, the authors investigated the relationships among the average contents of calcium, phosphorus, sulfur, and magnesium in the 18 kinds of the Thai artery. After ordinary dissection by medical students at Chiang Mai University was finished, the thoracic and abdominal aortas, ramifying site of the abdominal aorta into the common iliac arteries, coronary, common carotid, internal thoracic, subclavian, axillary, brachial, radial, superior and inferior mesenteric, renal, common iliac, internal iliac, and external iliac arteries were resected from the subjects who consisted of 12 men and 3 women, ranging in age from 39 to 84 yr. The femoral and posterior tibial arteries were resected from the subjects, consisting of 15 men and 5 women, ranging in age from 25 to 88 yr. The element content of the arteries was analyzed by inductively coupled plasma-atomic emission spectrometry. It was found that there were extremely significant direct correlations among the average contents of calcium, phosphorus, and magnesium in the 18 kinds of the Thai artery, but no significant correlations were found between the average contents of sulfur and elements, such as calcium, phosphorus, and magnesium. These results were in agreement with those of the Japanese arteries. Therefore, it was suggested that there was no significant difference between the arteries of the Thai and the Japanese in the relationships among calcium, phosphorus, sulfur, and magnesium.     

The mechanism of fibril formation of a non-inhibitory serpin ovalbumin revealed by the identification of amyloidogenic core regions

Ovalbumin (OVA), a non-inhibitory member of the serpin superfamily, forms fibrillar aggregates upon heat-induced denaturation. Recent studies suggested that OVA fibrils are generated by a mechanism similar to that of amyloid fibril formation, which is distinct from polymerization mechanisms proposed for other serpins. In this study, we provide new insights into the mechanism of OVA fibril formation through identification of amyloidogenic core regions using synthetic peptide fragments, site-directed mutagenesis, and limited proteolysis. OVA possesses a single disulfide bond between Cys(73) and Cys(120) in the N-terminal helical region of the protein. Heat treatment of disulfide-reduced OVA resulted in the formation of long straight fibrils that are distinct from the semiflexible fibrils formed from OVA with an intact disulfide. Computer predictions suggest that helix B (hB) of the N-terminal region, strand 3A, and strands 4-5B are highly β-aggregation-prone regions. These predictions were confirmed by the fact that synthetic peptides corresponding to these regions formed amyloid fibrils. Site-directed mutagenesis of OVA indicated that V41A substitution in hB interfered with the formation of fibrils. Co-incubation of a soluble peptide fragment of hB with the disulfide-intact full-length OVA consistently promoted formation of long straight fibrils. In addition, the N-terminal helical region of the heat-induced fibril of OVA was protected from limited proteolysis. These results indicate that the heat-induced fibril formation of OVA occurs by a mechanism involving transformation of the N-terminal helical region of the protein to β-strands, thereby forming sequential intermolecular linkages.     

Activation of caspase 3 in HepG2 cells by elaidic acid (t18:1)

In order to examine the effects of trans-unsaturated fatty acids (TFAs) on HepG2 cells, cells were grown in serum-free media supplemented with elaidic acid (t18:1); t18:1 is the trans-isomer of oleic acid and is the major component of TFAs in foods. Both t18:1 and palmitic acids (16:0) at concentrations higher than 100 microM inhibited growth and decreased the rate of protein synthesis. The presence of phosphatidylserine in the outer leaflet of the lipid bilayer, indicative of apoptosis, occurred 1 h after the addition of both t18:1 and 16:0 to the media. Caspase 3 was found to be activated by these fatty acids: caspase 8 was activated by 16:0 and only moderately by t18:1. Activation of caspase 3 by these fatty acids was fully inhibited by a caspase 8 inhibitor. However, growth inhibition by t18:1 was partially prevented by the caspase 8 inhibitor. These results suggest that cell death caused by t18:1 may proceed by both caspase-dependent and -independent pathways.     

Mechanism of photoisomerization of optically pure trans-2,3-diphenylcyclopropane-1-carboxylic acid derivatives.

The photochemistry of optically pure isomers of alpha-methylbenzylamide of trans-2,3-diphenylcyclopropane-1-carboxylic acid has been examined in isotropic solution and within zeolites. The results suggest that these isomerize through cleavage of C2-C3 bond. The direct excitation in solution leads to non-equilibrating 1,3-singlet diradical intermediates whereas triplet sensitization results in equilibrating 1,3-triplet diradical intermediates. The direct excitation within NaY zeolite seems to result in equilibrating zwitterionic intermediates. Studies on the optically pure trans isomers allow one to understand the mechanism of chiral induction during the photoisomerization of mesocis-2,3-diphenylcyclopropane-1-carboxylic acid. The current study has clarified the nature of the excited states involved during the classic (R)-N-acetyl-1-naphthylethylamine sensitized isomerization of 1,2-diphenylcyclopropane.     

Purification and Some Properties of Soluble Cytochromes, Cytochrome c-551 and Cytochrome c-550, from a Facultative Methylotroph, Protaminobacter ruber strain NR-1

Two soluble cytochromes of the C-type, cytochrome c-551 andcytochrome c-550, were purified from the bacteriochlorophyll-containingcells of a facultative methylotroph, Protaminobacter ruber StrainNR-1, by ion-exchange chromatography and gel-filtration. Cytochrome c-551 had absorption maxima at 551, 522 and 416 nmin the reduced form, and at 525, 410 and 273 nm in the oxidizedform. This cytochrome was a slightly basic protein with an isoelectricpoint of 8.4. It had a mid-point redox potential of 272 mV atpH 7.0. The molecular weight of this protein was 13,500 and13,700 by sodium dodecylsulfate polyacrylamide gel electrophoresis(SDS-PAGE) and gel-filtration, respectively. Cytochrome c-550 had absorption maxima at 550, 522 and 415 nmin the reduced form, and at 527, 409 and 278 nm in the oxidizedform. This cytochrome was acidic, having an isoelectric pointof 4.3. It had a mid-point redox potential of 227 mV at pH 7.0.Its molecular weight was 19,500 and 22,000 by SDS-PAGE and gel-filtration,respectively. (Received August 4, 1984; Accepted October 22, 1984)