Probability in biology: Overview of a comprehensive theory of probability in living systems

Probability is closely related to biological organization and adaptation to the environment. Living systems need to maintain their organizational order by producing specific internal events non-randomly, and must cope with the uncertain environments. These processes involve increases in the probability of favorable events for these systems by reducing the degree of uncertainty of events. Systems with this ability will survive and reproduce more than those that have less of this ability. Probabilistic phenomena have been deeply explored using the mathematical theory of probability since Kolmogorov's axiomatization provided mathematical consistency for the theory. However, the interpretation of the concept of probability remains both unresolved and controversial, which creates problems when the mathematical theory is applied to problems in real systems. In this article, recent advances in the study of the foundations of probability from a biological viewpoint are reviewed, and a new perspective is discussed toward a comprehensive theory of probability for understanding the organization and adaptation of living systems.     

Denitrification in soil amended with thermophile-fermented compost suppresses nitrate accumulation in plants

NO ₃ ^? is a major nitrogen source for plant nutrition, and plant cells store NO ₃ ^? in their vacuoles. Here, we report that a unique compost made from marine animal resources by thermophiles represses NO ₃ ^? accumulation in plants. A decrease in the leaf NO ₃ ^? content occurred in parallel with a decrease in the soil NO ₃ ^? level, and the degree of the soil NO ₃ ^? decrease was proportional to the compost concentration in the soil. The compost-induced reduction of the soil NO ₃ ^? level was blocked by incubation with chloramphenicol, indicating that the soil NO ₃ ^? was reduced by chloramphenicol-sensitive microbes. The compost-induced denitrification activity was assessed by the acetylene block method. To eliminate denitrification by the soil bacterial habitants, soil was sterilized with γ irradiation and then compost was amended. After the 24-h incubation, the N₂O level in the compost soil with presence of acetylene was approximately fourfold higher than that in the compost soil with absence of acetylene. These results indicate that the low NO ₃ ^? levels that are often found in the leaves of organic vegetables can be explained by compost-mediated denitrification in the soil.     

A novel,potent, and orally active VLA-4 antagonist with good aqueous solubility: trans-4-[1-[[2-(5-Fluoro-2-methylphenylamino)-7-fluoro-6-benzoxazolyl]acetyl]-(5S)-[methoxy(methyl)amino]methyl-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid

We have carried out the optimization of substituents at the C-3 or the C-5 position on the pyrrolidine ring of VLA-4 antagonist 3 with 2-(phenylamino)-7-fluorobenzoxazolyl moiety for the purpose of improving in vivo efficacy while maintaining good aqueous solubility. As a result, we successfully increased in vitro activity in the presence of 3% human serum albumin and achieved an exquisite lipophilic and hydrophilic balance of compounds suitable for oral administrative regimen. The modification resulted in the identification of zwitterionic compound 7n with (5S)-[methoxy(methyl)amino]methylpyrrolidine, which significantly alleviated bronchial hyper-responsiveness to acetylcholine chloride at 12.5 mg/kg, p.o. in a murine asthma model and showed favorable aqueous solubility (JP1, 89 μg/mL; JP2, 462 μg/mL). Furthermore, this compound showed good oral bioavailability (F = 54%) in monkeys.     

Ester Synthesis in Various Organic Solvents by Three Kinds of Lipase Preparations Derived from Pseudomonas fragi 22.39 B

DNA-synthesis stimulatory activity was found in some tryptic fragments of human /¡-casein by using BALB/c3T3 cells, and two of them were identified as the /¡-casein fragments of Arg[l] to Lys[18] (/¡-CN(f 1 -18)) and of Gln[105] to Lys[l 17] (/¡-CN(fl05 -117)).     

Purification and Properties of a New l-Fucose-specific Lectin Produced by Streptomyces No. 100–2

The inhibitory effects of 3-nitro-2,4,6-trihydroxybenzamide derivatives on human 5-lipoxygenase (5-LO), a key enzyme in arachidonic acid cascades, were examined using 5-LO produced by Escherichia coli. Some of the tested compounds inhibited the conversion of arachidonic acid to 5-hydroperoxy-6,8,11,14-eicosatetraenoic acid (5-HPETE), and in particular the N-phenylbutyl derivative was about 30 times more active (IC₅₀ = 35 μm) than caffeic acid (IC₅₀ = 1000 μm), a known selective 5-LO inhibitor.     

Human Erythrocyte Receptor of l-Fucose-specific Lectin Produced by Streptomyces sp.

L-Fucose-specific lectin produced by Streptomyces no. 16-3 (SFL 16-3) was labeled with N- succinimidyl-[2, 3-³H]-propionate to quantitatively investigate its binding to human erythrocytes. The binding inhibition by sugars was competitive, and 5mM L-fucose or 20 mM d-mannose completely inhibited the binding. Among plant lectins, Lotus tetragonolobus, Ulex europeus I, soybean and wheat germ lectin showed competitive inhibition. The association constant and the average number of binding sites for human blood group O erythrocytes were approximately 3 × 10⁷ M^-1 and 1 × 10⁶ cell^-1, respectively. Trypsinization of erythrocytes preferentially increased the number of binding sites for human A and B erythrocytes but not for O erythrocytes.

Membrane components were extracted from human B and O erythrocytes and their binding activity for SFL 16-3 was tested using the hemagglutination-inhibition assay. Poly(glycosyl)-ceramide was the predominant receptor and its fucosyl residue was essential for binding. The crude glycoprotein fraction showed only slight inhibition activity.     

Production of Acetone and Butanol Using Immobilized Growing-cells of Clostridium acetobutylicum

The biosynthetic route for chloromonilicin, an antifungal substance from cherry rot fungus, was investigated using deuterium-labeled precursors. The incorporation of synthetic deuterium-labeled moniliphenone into chloromonilicin and into its xanthone precursor, 4-chloropinselin, was confirmed by ’H-NMR spectrometry.     

Purification and Properties of Polyol: NADP Oxidoreductase from Pichia quercuum

In order to explain the fermentation mechanism of xylitol production from d-xylose by Pichia quercuum, enzymatic study was carried out. Three kinds of enzymes that catalyzed the reduction of d-xylose to xylitol were purified from the extract of the yeast cells by ammonium sulfate fractionation, Sephadex G-200 gel filtration, hydroxylapatite chromatography and disc electrophoresis. The purification showed 27-fold, 135-fold and 93-fold increases of specific activities of reductase I, IIa and lib, respectively, over the crude extract. The reductase Ha was homogeneous in disc gel electrophoresis. The activity ratio of reductase I: IIa: IIb in the crude extract was estimated to be approximately 2: 1:1. The three enzymes were active with a variety of aldoses and had a specific requirement for NADPH. On the basis of the substrate specificity, coenzyme requirement and the stoichiometry of the reaction, the enzymes belong to polyol: NADP oxidoreductase (EC 1.1.1.21, trivial name, aldose reductase). The molecular weights for reductase I, IIa and IIb were estimated to be 160,000, 61,000 and 61,000, respectively, by gel filtration. Disc gel electrophoresis suggested that reductase Ila and lib were charge isomeric proteins with the same molecular size. Some other properties of the three enzymes were also described.     

Methyl-β-cyclodextrin potentiates the BITC-induced anti-cancer effect through modulation of the Akt phosphorylation in human colorectal cancer cells

ABSTRACT

Methyl-β-cyclodextrin (MβCD) is an effective agent for the removal of plasma membrane cholesterol. In this study, we investigated the modulating effects of MβCD on the antiproliferation induced by benzyl isothiocyanate (BITC), an ITC compound mainly derived from papaya seeds. We confirmed that MβCD dose-dependently increased the cholesterol level in the medium, possibly through its removal from the plasma membrane of human colorectal cancer cells. The pretreatment with a non-toxic concentration (2.5 mM) of MβCD significantly enhanced the BITC-induced cytotoxicity and apoptosis induction, which was counteracted by the cholesterol supplementation. Although BITC activated the phosphoinositide 3-kinase (PI3K)/Akt pathway, MβCD dose-dependently inhibited the phosphorylation level of Akt. On the contrary, the treatment of MβCD enhanced the phosphorylation of mitogen activated protein kinases, but did not potentiate their BITC-induced phosphorylation. These results suggested that MβCD might potentiate the BITC-induced anti-cancer by cholesterol depletion and thus inhibition of the PI3K/Akt-dependent survival pathway.

Abbreviations: CDs: cyclodextrins; MβCD: methyl-β-cyclodextrin; ITCs: isothiocyanates; BITC: benzyl isothiocyanate; PI3K: phosphoinositide 3-kinase; PDK1: phosphoinositide-dependent kinase-1; MAPK: mitogen activated protein kinase; ERK1/2: extracellular signal-regulated kinase1/2; JNK: c-Jun N-terminal kinase; PI: propidium iodide; FBS: fatal bovine serum; TLC: thin-layer chromatography; PBS(-): phosphate-buffered saline without calcium and magnesium; MEK: MAPK/ERK kinase; PIP2: phosphatidylinositol-4,5-bisphosphate; PIP3: phosphatidylinositol-3,4,5-trisphosphate