Lateral interactions among phosphatidylcholine and phosphatidylethanolamine head groups in phospholipid monolayers and bilayers

We develop theory for the lateral interactions among the zwitterionic head groups of phospholipids in monolayers and bilayers, particularly phosphatidylcholine (PC) and phosphatidylethanolamine (PE). With the P- end of the head group anchored at the water/hydrocarbon interface, a balance of two effects dictates the angle that the P--N+ dipole makes with respect to the plane of the bilayer: N+ is driven toward water due to the (Born) electrostatic free energy, but the hydrophobic effect drives the methyl and methylene groups around the N+ charge toward the hydrocarbon. The only adjustable parameter of the model is the average fluctuation of the oil/water interface or, alternatively, the dielectric constant of the hydrocarbon phase. The model predicts that at 5 degrees C the head group dipole should lie largely in the bilayer plane, in accord with X-ray, neutron diffraction, and NMR studies. The theory makes the novel prediction that the N+ end of the dipole becomes increasingly submerged in hydrocarbon with increasing temperature, leading to strongly enhanced lateral repulsion between PC head groups. This prediction is in good agreement with second and third viral coefficients of monolayer lateral pressures, and with the temperature dependence of the former. The theoretical model is consistent with head group fluctuations measured by neutron diffraction of PC and PE bilayers. Because PE has a smaller hydrophobic cluster near N+, its lateral repulsion should be much smaller and less temperature dependent than for PC, also in agreement with equation-of-state measurements. This suggests why at high density PE monolayers have higher melting temperatures than PC monolayers and more propensity for reversed curvature.     

The Evolution of Restricted Recombination and the Accumulation of Repeated DNA Sequences

We suggest hypotheses to account for two major features of chromosomal organization in higher eukaryotes. The first of these is the general restriction of crossing over in the neighborhood of centromeres and telomeres. We propose that this is a consequence of selection for reduced rates of unequal exchange between repeated DNA sequences for which the copy number is subject to stabilizing selection: microtubule binding sites, in the case of centromeres, and the short repeated sequences needed for terminal replication of a linear DNA molecule, in the case of telomeres. An association between proximal crossing over and nondisjunction would also favor the restriction of crossing over near the centromere. The second feature is the association between highly repeated DNA sequences of no obvious functional significance and regions of restricted crossing over. We show that highly repeated sequences are likely to persist longest (over evolutionary time) when crossing over is infrequent. This is because unequal exchange among repeated sequences generates single copy sequences, and a population that becomes fixed for a single copy sequence by drift remains in this state indefinitely (in the absence of gene amplification processes). Increased rates of exchange thus speed up the process of stochastic loss of repeated sequences.     

Identification of the major endogenous leukotriene metabolite in the bile of rats as N-acetyl leukotrience E4

Mercapturic acid formation, an established pathway in the detoxication of xenobiotics, is demonstrated for cysteinyl leukotrienes generated in rats after endotoxin treatment. The mercapturate N-acetyl-leukotriene E₄ (N-acetyl-LTE₄) represented a major metabolite eliminated into bile after injection of [³H]LTC₄ as shown by cochromatography with synthetic N-acetyl-LTE₄ in four different HPLC solvent systems. The identity of endogenoud N-acetyl-LTE₄ elicited by endotoxin was additionally verified by enzymatic deacetylation followed by chemical N-acetylation. The deacetylation was catalyzed by penicillin amidase. Endogenous cysteinyl leukotrienes were quantified by radioimmunoassay after HPLC separation. A N-acetyl-LTE₄ concentration of 80 nmol/l was determined in bile collected between 30 and 60 min after endotoxin injection. Under this condition, other cysteinyl leukotrienes detected in bile by radioimmunoassay amounted to less than 5% of N-acetyl-LTE₄. The mercapturic acid pathway, leading from the glutathione conjugate LTC₄ to N-acetyl-LTE₄, thus plays an important role in the deactivation and elimination of these potent endogenous mediators.     

31P nuclear magnetic resonance study of enzymatically phosphorylated glycophorin A

Glycophorin A was phosphorylated using protein kinases and the new protein was investigated using³¹P NMR spectroscopy. Most of these ～30 moles of phosphate were found to be attached to Ser and Thr. Some of these phosphate residues appear to be affected by the carbohydrate residues present. The phosphorylated protein appears to be in a severe state of aggregation, with the degree of aggregationpH-dependent.     

Volume comparisons in the cerebellar complex of primates. II. Cerebellar nuclei

Volumes of medial, interposed, and lateral cerebellar nuclei (MCN, ICN, and LCN) were measured in Insectivora, Scandentia, and Primates, including man. The relative size of the nuclei was expressed in size indices. Insectivora had by far the smallest cerebellar nuclei. The simians, in general, had larger cerebellar nuclei than the prosimians, but there was considerable overlap. From Insectivora to man, the MCN was the least progressive and the LCN the most progressive. The indices are expected to reflect the relative size of the three longitudinal zones of the cerebellum (vermis/MCN, pars intermedius/ICN, hemisphere/LCN). They, together with those of the ventral pons and cerebellum (part I), are discussed in relation to the predominant locomotor pattern of a species, and with reference to evolutionary trends in primate phylogeny.     

Determination of the hydraulic conductivity of Lamprothamnium by use of the pressure clamp

By use of the pressure-clamp technique, the hydraulic conductivity of the brackish-water alga Lamprothamnium was found to be 5·10^-6 cm s^-1 bar^-1. The dimensions of the internodes are so small that it is possible, for the first time, to measure a complete volume relaxation upon clamping the turgor pressure to a preset value by a feedback control of the pressure probe. As theoretically predicted, the values of the hydraulic conductivity obtained from the initial slope of the volume relaxation induced by the pressure clamp are in agreement (within experimental error) with those obtained from the half-time of the relaxation process. The cell volume also obtained from the analysis of the volume relaxation is the osmotically effective cell volume and is therefore slightly smaller than the value obtained by taking the dimensions of the cell including the cell wall.Abbreviations and symbols Lp hydraulic conductivity - P turgor pressure - S_v initial slope of volume relaxion - T_1/2 half-time of volume relaxation Dedicated to Professor Dr. H. Ziegler on the occasion of his 60th birthday     

The role of insulin, glucagon and growth hormone in the regulation of plasma glucose and free fatty acid levels in anorexia nervosa

It is well established that glucagon plays an important role in the regulation of fuel supplies as its plasma level increases during the first days of a complete fast. However, it is not certain that glucagon is involved in the adaptation to chronic starvation. In the present study, this problem was investigated by the determination of the changes in the plasma glucagon level elicited by an i.v. glucose tolerance test followed by an i.v. arginine perfusion in 26 self starved patients suffering from anorexia nervosa (AN) and 14 control patients having only minor neurotic disorders. The basal plasma glucagon level tended to be higher in the AN patients than in the controls; but the difference was not statistically significant. Glucagon responses to glucose and arginine observed in the AN patients were not significantly different from those seen in the control patients. In the AN patients, the insulin response to both loads was reduced and the plasma GH level increased paradoxically after the glucose load, whereas it rose normally after the arginine load. It may be concluded that in chronic starvation by AN the regulation of fuel supplies depends mainly on decreased insulin and increased growth hormone secretion. The role of glucagon seems to be of minor importance in this condition.     

Electrorotation of lymphocytes—The influence of membrane events and nucleus

Electrorotation—the spin of cells in rotating high frequency electric fields—has been used to investigate properties of human peripheral blood lymphocytes. The rotation spectra of lymphocytes deviate from those of single shell spheres. The deviations are caused by the electrical properties of the nucleus in the cell interior.Electrorotation allows the distinction between successfully stimulated lymphocytes and unstimulated cells after application of concanavalin A. Notwithstanding the fact that only a proportion of the cells will be mitogenically stimulated we detected an enhanced cell membrane conductivity for the whole cell population immediately after the addition of mitogen.     

Rate theory models for ion transport through rigid pores. I. Time-dependent analysis in the case of vanishing interactions

In this first of a series of papers concerning the theoretical analysis of rate theory models for ion transport through rigid pores, the case of vanishing interactions is investigated. "Rigidity" means that ions crossing membranes through pores see a fixed structure of the pores, not changing in time. A single pore is considered to be a sequence of (n + 1) activation barriers separated by n energy minima. The explicit analytical treatment is restricted to pores with regular internal barrier structure, including the nonequilibrium situation of an applied electric field. In this case the connection with continuum diffusion models is demonstrated by performing in the limit n leads to infinity (n = number of binding sites within the pores) the transition to continuum. Thus, from diffusion equations describing a discrete number of jumps, the corresponding diffusion-like partial differential equations and boundary conditions are generated. For regular pores, from the time dependent solutions of the discrete equations, the corresponding solutions of the continuum equations are explicitly generated. The time-dependent relaxation behaviour of the discrete model is in good agreement with the continuum model if one assumes more than two binding sites in the pores.