Cellular systems as sequential machines: Stability properties

In previous studies of (M,R) (Rosen, 1961; Demetrius, 1966), it was assumed that changes in the structure of (M,R) which were induced by environmental alternations occurred without error. Here, the effect of both “genetic” and “metabolic” malfunctions on the behavior of (M,R) is examined and a subclass of these systems whose behavior is invulnerable to such errors is specified.     

Contributions to relational biology

The principle of biotopological mapping (Rashevsky, 1954,Bull. Math. Biophysics,16, 317–48) is given a generalized formulation, as the principle of relational epimorphism in biology. The connection between this principle and Robert Rosen’s representation of organisms by means of categories (1958,Bull. Math. Biophysics,20, 317–41) is studied. Rosen’s theory of (M,R)-systems, (1958,Bull. Math. Biophysics,20, 245–60) is generalized by dropping the assumption that only terminalM _i components are sending inputs into theR _i components. It is shown that, if the primordial organism is an (M,R)-system, then the higher organisms, obtained by a construction well discussed previously (1958,Bull. Math. Biophysics,20, 71–93), are also (M,R)-systems. Several theorems about such derived (M,R)-systems are demonstrated. It is shown that Rosen’s concept of an organism as a set of mappings throws light on phenomena of synesthesia and also leads to the conclusion that Gestalt phenomena must occur not only in the fields of visual and auditory perception but in perceptions of any modality.     

Abstract biological systems as sequential machines: Behavioral reversibility

Rosen’s identification of abstract biological systems, called (M,R)-systems, with sequential machines is formally characterized. It is then shown that the determination of environmental alterations of (M,R)-systems from a knowledge of the response sequence and the structure of the system, which we call behavioral reversibility, can be interpreted as information-losslessness of sequential machines. Applying this relationship, necessary conditions for behavioral reversibility are derived. It is further shown that, similar to Rosen’s work on structural reversibility, (M,R)-systems are behaviorally reversible only if the number of physically realizable mappings are restricted.     

Divergent scaling of respiration rates to nitrogen and phosphorus across four woody seedlings between different growing seasons

Empirical studies indicate that the exponents governing the scaling of plant respiration rates (R) with respect to biomass (M) numerically vary between three‐fourth for adult plants and 1.0 for seedlings and saplings and are affected by nitrogen (N) and phosphorus (P) content. However, whether the scaling of R with respect to M (or N and P) varies among different phylogenetic groups (e.g., gymnosperms vs. angiosperms) or during the growing and dormant seasons remains unclear. We measured the whole‐plant R and M, and N and P content of the seedlings of four woody species during the growing season (early October) and the dormant season (January). The data show that (i) the scaling exponents of R versus M, R versus N, and R versus P differed significantly among the four species, but (ii), not between the growing and dormant seasons for each of the four species, although (iii) the normalization constants governing the scaling relationships were numerically greater for the growing season compared to the dormant season. In addition, (iv) the scaling exponents of R versus M, R versus N, and R versus P were numerically larger for the two angiosperm species compared to those of the two gymnosperm species, (v) the interspecific scaling exponents for the four species were greater during the growing season than in the dormant season, and (vi), interspecifically, P scaled nearly isometric with N content. Those findings indicate that the metabolic scaling relationships among R, M, N, and P manifest seasonal variation and differ between angiosperm and gymnosperm species, that is, there is no single, canonical scaling exponent for the seedlings of woody species.     

Allometric scaling relationship between above‐ and below‐ground biomass within and across five woody seedlings

Allometric biomass allocation theory predicts that leaf biomass (M_L) scaled isometrically with stem (M_S) and root (M_R) biomass, and thus above‐ground biomass (leaf and stem) (M_A) and root (M_R) scaled nearly isometrically with below‐ground biomass (root) for tree seedlings across a wide diversity of taxa. Furthermore, prior studies also imply that scaling constant should vary with species. However, litter is known about whether such invariant isometric scaling exponents hold for intraspecific biomass allocation, and how variation in scaling constants influences the interspecific scaling relationship between above‐ and below‐ground biomass. Biomass data of seedlings from five evergreen species were examined to test scaling relationships among biomass components across and within species. Model Type II regression was used to compare the numerical values of scaling exponents and constants among leaf, stem, root, and above‐ to below‐ground biomass. The results indicated that M_L and M_S scaled in an isometric or a nearly isometric manner with M_R, as well as M_A to M_R for five woody species. Significant variation was observed in the Y‐intercepts of the biomass scaling curves, resulting in the divergence for intraspecific scaling and interspecific scaling relationships for M_L versus M_S and M_L versus M_R, but not for M_S versus M_R and M_A versus M_R. We conclude, therefore, that a nearly isometric scaling relationship of M_A versus M_R holds true within each of the studied woody species and across them irrespective the negative scaling relationship between leaf and stem.     

Absolute configurations and CD spectra of axially chiral biphenyls prepared in a facile manner by crystallization‐induced configuration transformation

Axially chiral biphenyls such as (M,S)‐ 3k have been conveniently obtained by crystallization of their diastereomeric mixtures, which were synthesized from racemic 4,4′‐dimethoxy‐5,6,5′,6′‐bis(methylenedioxy)‐2‐carboxylester‐2′‐carboxyl‐biphenyls 4 and chiral amino alcohols (R)‐alaninol, (S)‐alaninol, (S)‐valinol, and (S)‐phenylalaninol. A crystallization‐induced configuration transformation of the biphenyls was thus achieved. It was found that amide formation of an (S)‐valinol or (S)‐phenylalaninol at the 2′‐position of the biphenyl usually induced the deposition of crystals with the (M)‐configuration from ethanol in yields higher than 50%. The absolute configurations (ACs) of two crystalline biphenyls have been determined by X‐ray crystallographic analysis. The ACs of nine biphenyls have been assigned based on their CD spectra. Further, stability investigation of these axially chiral biphenyls revealed that the ACs could revert upon redissolution. The energy barrier to epimerization between (P,R)‐ 3b and (M,R)‐ 3b was measured as ΔG^# = 21.45 kcal/mol and the half‐life in ethanol at 301 K was 17.1 h. Chirality, 2010. © 2010 Wiley‐Liss, Inc.     

Selective distortion of the planar group CαC'(O)O to a chiral flat tetrahedron in the amino acid alanine

Based on a Cambridge Structural Database (CSD) search, a meta‐analysis of 116 structures of alanine H₃NC_αH(CH₃)C′(O)O and its derivatives H₃NC_αH(CH₃)C′(O)O(H/R/M), protonated, esterified, or coordinated at the carboxylic group, shows that in the first step of a chirality chain, the L configuration at C_α induces (M) and (P) conformations with respect to rotation around the central C′─C_α bond. In the second step, the (M) and (P) conformations selectively distort the planar carboxylic group C_αC'(O_cis)O_trans to asymmetric flat (R) and (S) tetrahedra. High diastereoselectivities are caused by the two players attraction N…O_cis and repulsion O_trans…C_Me, which work together in (L,M,R) configurations but against each other in (L,P,S) configurations.     

Standard metabolism and growth dynamics of laboratory‐reared larvae of Sardina pilchardus

This study provides the first measurements of the standard respiration rate (R_S) and growth dynamics of European sardine Sardina pilchardus larvae reared in the laboratory. At 15° C, the relationship between R_S (µl O₂ individual^?1 h^?1) and larval dry mass (M_D, µg) was equal to: R_S = 0·0057(±0·0007, ± s.e.)·M_D^{0·8835(±0·0268)}, (8–11% M_D day^?1). Interindividual differences in R_S were not related to interindividual differences in growth rate or somatic (Fulton's condition factor) or biochemical‐based condition (RNA:DNA).     

A novel enzymatic dehalogenation of (R)-3-chloro-1,2-propanediol inAlcaligenes sp. DS-S-7G

The mechanism of the novel enzymatic dehalogenating action of (R)-3-chloro-1,2-propanediol [monochlorohydrin (MCH)] was investigated. The (R)-MCH-dechlorinating enzyme system ofAlcaligenes sp. DS-S-7G, which stereoselectively assimilated (R)-MCH from the racemate, was composed of two components (Enzyme 1 and Enzyme 2). Enzyme 1 was a flavoprotein with a relative molecular mass (M _r) of 70,000 and was composed of two kinds of polypeptides (58,000 and 16,000). The enzyme exhibited activity for converting (R)-MCH to hydroxyacetone with the liberation of chloride ions under aerobic conditions. On the other hand, Enzyme 2 with anM _r of 86,000, which was also composed of two kinds of polypeptides (33,000 and 53,000), showed no dechlorinating activity for (R)-MCH. However, in the presence of NAD⁺, when Enzyme 1 was conjugated with Enzyme 2 in the (R)-MCH-dechlorinating reaction, the co-operative dechlorinating activity was four to five times higher than that by Enzyme 1 alone. (R)-MCH was finally degraded to acetic acid and formic acid by the joint action of the two enzymes. These facts indicate that (R)-MCH is oxidatively dechlorinated by the two enzymes in the presence of NAD⁺ inAlcaligenes sp. DS-S-7G.     

Approximate matching of regular expressions

Given a sequenceA and regular expressionR, theapproximate regular expression matching problem is to find a sequence matchingR whose optimal alignment withA is the highest scoring of all such sequences. This paper develops an algorithm to solve the problem in timeO(MN), whereM andN are the lengths ofA andR. Thus, the time requirement is asymptotically no worse than for the simpler problem of aligning two fixed sequences. Our method is superior to an earlier algorithm by Wagner and Seiferas in several ways. First, it treats real-valued costs, in addition to integer costs, with no loss of asymptotic efficiency. Second, it requires onlyO(N) space to deliver just the score of the best alignment. Finally, its structure permits implementation techniques that make it extremely fast in practice. We extend the method to accommodate gap penalties, as required for typical applications in molecular biology, and further refine it to search for substrings ofA that strongly align with a sequence inR, as required for typical data base searches. We also show how to deliver an optimal alignment betweenA andR in onlyO(N+logM) space usingO(MN logM) time. Finally, anO(MN(M+N)+N ²logN) time algorithm is presented for alignment scoring schemes where the cost of a gap is an arbitrary increasing function of its length.     

Novel life‐history data for threatened seahorses provide insight into fishery effects

Life‐history variables for three incidentally captured species of seahorse (Kellogg's seahorse Hippocampus kelloggi, the hedgehog seahorse Hippocampus spinosissimus and the three‐spot seahorse Hippocampus trimaculatus) were established using specimens obtained from 33 fisheries landing sites in Peninsular Malaysia. When samples were pooled by species across the peninsula, sex ratios were not significantly different from unity, and height and mass relationships were significant for all species. For two of these species, height at physical maturity (H_M) was smaller than the height at which reproductive activity (H_R) commenced: H. spinosissimus (H_M = 99·6 mm, H_R = 123·2 mm) and H. trimaculatus (H_M = 90·5 mm, H_R = 121·8 mm). For H. kelloggi, H_M could not be estimated as all individuals were physically mature, while H_R = 167·4 mm. It appears that all three Hippocampus spp. were, on average, caught before reproducing; height at 50% capture (H_C) was ≥H_M but ≤H_R. The results from this study probe the effectiveness of assessment techniques for data‐poor fisheries that rely heavily on estimates of length at maturity, especially if maturity is poorly defined. Findings also question the sustainability of H. trimaculatus catches in the south‐west region of Peninsular Malaysia, where landed specimens had a notably smaller mean height (86·2 mm) and markedly skewed sex ratio (6% males) compared with samples from the south‐east and north‐west of the peninsula.     

Light scattering and viscosity study of heat aggregation of insulin

Aggregation behavior and hydrodynamic parameters of insulin have been determined from static and dynamic light scattering experiments and intrinsic viscosity measurements carried out at pH 4.0, 7.5, and 9.0 in the temperature range 20–40°C in aqueous solutions. The protein aggregated extensively at elevated temperatures in the acidic solutions. Intermolecular interactions were found to be attractive and to increase with temperature. The measured intrinsic viscosity [η], diffusion coefficient D₀, molecular weight M, and radius of gyration R_g exhibited the universal behavior: M[η] = (2.4 ± 02) × 10⁻²⁷ (R_e,η/R_e,D)³(D_0η/T)⁻³ and (D₀√n)₋₁ ≃ (√6 πη₀ζβ/k_BT) [1 + 0.201)(v/β³)√n], where n is the number of segments in the polypeptide. The effective hydrodynamic radii deduced from [η], (R_e, η) and the same deduced from D₀, (R_e,D) showed a constant ratio, (R_e,η/R_e,D = 1.1 ± 0.1). R_e,D/R_g = ξ was found to be (0.76 ± 0.07). From the known solvent viscosity η₀, the segment length β was deduced to be (10 ± 1) Å. The excluded volume was deduced to be (5 Å)³ regardless of pH. The Flory-Huggins interaction parameter was found to be χ = 0.45 ± 0.04, independent of pH and temperature. © 1998 John Wiley & Sons, Inc. Biopoly 45: 1–8, 1998     

Characterization of (2S,2'R,3'R)-2-(2',3'-[3H]-Dicarboxycyclopropyl)glycine Binding in Rat Brain

Abstract: [(2S,2′R,3′R)-2-(2′,3′-[³H]Dicarboxycyclopropyl)glycine ([³H]DCG IV) binding was characterized in vitro in rat brain cortex homogenates and rat brain sections. In cortex homogenates, the binding was saturable and the saturation isotherm indicated the presence of a single binding site with a K_D value of 180 ± 33 nM and a B_max of 780 ± 70 fmol/mg of protein. The nonspecific binding, measured using 100 µM LY354740, was <30%. NMDA, AMPA, kainate, l (?)-threo-3-hydroxyaspartic acid, and (S)-3,5-dihydroxyphenylglycine were all inactive in [³H]DCG IV binding up to 1 mM. However, several compounds inhibited [³H]DCG IV binding in a concentration-dependent manner with the following rank order of potency: LY341495 = LY354740 > DCG IV = (2S,1′S,2′S)-2-(2-carboxycyclopropyl)glycine > (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid > (2S,1′S,2′S)-2-methyl-2-(2-carboxycyclopropyl)glycine > l -glutamate = ibotenate > quisqualate > (RS)-α-methyl-4-phosphonophenylglycine = l (+)-2-amino-3-phosphonopropionic acid > (S)-α-methyl-4-carboxyphenylglycine > (2S)-α-ethylglutamic acid > l (+)-2-amino-4-phosphonobutyric acid. N-Acetyl-l -aspartyl-l -glutamic acid inhibited the binding in a biphasic manner with an IC₅₀ of 0.2 µM for the high-affinity component. The binding was also affected by GTPγS, reducing agents, and CdCl₂. In parasagittal sections of rat brain, a high density of specific binding was observed in the accessory olfactory bulb, cortical regions (layers 1, 3, and 4 > 2, 5, and 6), caudate putamen, molecular layers of the hippocampus and dentate gyrus, subiculum, presubiculum, retrosplenial cortex, anteroventral thalamic nuclei, and cerebellar granular layer, reflecting its preferential (perhaps not exclusive) affinity for pre- and postsynaptic metabotropic glutamate mGlu2 receptors. Thus, the pharmacology, tissue distribution, and sensitivity to GTPγS show that [³H]DCG IV binding is probably to group II metabotropic glutamate receptors in rat brain.     

Measurements of larval Atlantic cod (Gadus morhua) routine metabolism: temperature effects, diel differences and individual-based modeling

In the present study, dry mass (M_D, μg) and routine respiration rate (R_R) (μl O₂ ind^?1 h^?1) were measured for larval cod, Gadus morhua (L.) that were reared and tested at 5.0, 7.5, and 10.0°C. Bi‐hourly measurements of R_R were made on groups of larvae using a closed‐circuit respirometer over a 24‐h period (14L : 10D light regime) to test temperature and body size effects and whether unfed larvae exhibited diel differences in metabolism. At 10°C, the relationship between mean R_R and mean M_D was: ln R_R = 1.16·lnM_D ? 6.57 (n = 31, r² = 0.883, P < 0.001). The exponential increase in R_R with temperature was described by a Q₁₀ of 3.00. Diel differences in unfed larvae were only apparent in groups of the largest larvae. A comparison of Q₁₀ estimates from this and other studies suggest a linear decrease in the effect of temperature on cod R_R with increasing log M_D for sizes encompassing larvae to large juveniles. The trend may explain, in part, observations of cod juveniles exploiting a wider range of in situ temperatures than larvae. Finally, the two most comprehensive data sets on larval cod R_R compare poorly (approximately five‐fold differences) and our results support the assertion that daily metabolic energy loss in many larval cod individual‐based models were based upon measurements that over‐estimated hourly metabolic rates by a factor of approximately four.     

Synthesis of hydantoin analogues of (2S,3R,4S)-4-hydroxyisoleucine with insulinotropic properties

The first synthesis of an optically pure (2R,3R,4S)-hydantoin 2, analogue of (2S,3R,4S)-4-hydroxyisoleucine, was achieved in two steps in un-optimized 35% overall yield from previously reported aldehyde synthon 1. (2R,3R,4S)-Hydantoin is stable at acidic pH. This solves the major drawback of (2S,3R,4S)-4-hydroxyisoleucine that easily cyclizes into inactive lactone. Furthermore, (2R,3R,4S)-hydantoin stimulates the insulin secretion by 150% at 25 μM compared with 4-hydroxyisoleucine and insulin secretagogue drug repaglinide. In view of its stability and biological activity, (2R,3R,4S)-hydantoin represents a good candidate for type-2 diabetes management and control.     

Absolute configuration of eremophilane sesquiterpenes from Petasites hybridus: Comparison of experimental and calculated circular dichroism spectra

In‐depth conformational analyses of 10 known eremophilane (= (1S,4aR,7R,8aR)‐decahydro‐1,8a‐dimethyl‐7‐(1‐methylethyl)napththalene) sesquiterpenes, 1 – 10 , from Petasites hybridus were performed with molecular mechanics as well as density functional theory methods. Electronic transition energies and rotational strengths of these eight eremophilane lactones and two petasins were calculated by time‐dependent density functional theory (B3PW91/TZVP). The absolute configurations of the constituents could be assigned by comparison of their simulated and experimental circular dichroism (CD) spectra in methanol as (4S,5R,8S,10R) ( 1 , 2 ), (2R,4S,5R,8S,10R) ( 3 , 4 , 5 ), (2R,4S,5R,8R,9R,10R) ( 6 ), (2R,4S,5R,8R,10R) ( 7 , 8 ), and (3R,4R,5R) ( 9 , 10 ). Single‐crystal X‐ray diffraction data of 8β‐hydroxyeremophilanolide ((8S)‐8‐hydroxyeremophil‐7(11)‐en‐12,8‐olide) ( 1 ) served as starting point for the theoretical conformational calculations of the 8β‐epimers of the eremophilane lactones. Experimental CD spectra as well as ¹H NMR spectra of compound 1 in methanol were considerably dependent on sample concentration. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

Synthesis and nootropic activity of some 2,3-dihydro-1H-isoindol-1-one derivatives structurally related with piracetam

Three 2,3‐dihydro‐1H‐isoindol‐1‐ones structurally related with piracetam (=2‐oxopyrrolidine‐1‐acetamide) have been synthesized and tested for their nootropic effects in the passive avoidance test in mice. Compounds (RS)‐ 2 , (R,R)‐ 3 , and (R,S)‐ 3 were obtained in good yields in only two steps starting from methyl dl ‐phthaloylalanine. Compound (RS)‐ 2 exhibited nootropic activity at lower doses than piracetam, used as reference drug, but it showed lower efficacy. Whereas diastereoisomers (R,R)‐ 3 and (R,S)‐ 3 were as potent as piracetam to revert amnesia induced by scopolamine, (R,S)‐ 3 showed lower efficacy than (R,R)‐ 3 . Only (R,R)‐ 3 showed myorelaxant effect at doses of 10 and 30 mg/kg; other compounds did not exhibit any anticonvulsant, sedative, myorelaxant, or impaired motor‐coordination effect in mice. These synthesized 2,3‐dihydro‐1H‐isoindol‐1‐one derivatives constitute a new kind of nootropic compounds.     

Allometric relationship between body mass and aerobic metabolism in zebrafish Danio rerio

The relationship between body mass (M) and metabolic rate was investigated through the assessment of active (R_A) and standard (R_S) metabolic rate at different life stages in zebrafish Danio rerio (5 day‐old larvae, 2 month‐old juveniles and 6 month‐old adults). Scaling exponents and constants were assessed for standard (R_S = 0·273M^0·965 in mgO₂ g^?1 h^?1) and active metabolic rate (R_A = 0·799M^0·926 in mgO₂ g^?1 h^?1). These data provide the basis for further experiments regarding the effects of environmental factors on aerobic metabolism throughout the life cycle of this species.     

Cellular systems as graphs

The definition of an (M,R) is formulated in a way that emphasizes its mathematical properties. Neglecting interactions between the components, it is shown that:

1. An (M,R) contains only one non-reestablishable component.
2. If an (M,R) contains only one non-reestablishable component, then that component is central.

Examples are given to illustrate the biological significance of these two results. The notion of “lag-independence” is introduced, and it is shown that if a system possesses only one non-reestablishable component which is “lag-independent” then all components are lag-independent. The concepts of reestablishability, centrality and lag-independence are applied in order to suggest various criteria for optimal organization of (M,R).     

Biotransformation of zerumbone by <Emphasis Type="Italic">Caragana chamlagu</Emphasis>

Suspension cultured cells of Caragana chamlagu (Leguminosae) converted zerumbone (1) into zerumbone epoxide (2) as the intermediate, (2R,3R,7R)-2,3-epoxy-9-humulen-8-one (3) and (2R,3S,7R)-2,3-epoxy-9-humulen-8-one (4) as new sesquiterpenes in 11%, 36% and 21% yields, respectively.