E.s.r. of free radicals in irradiated uracil-beta-D-arabinofuranoside.

Electron-spin-resonance measurements have been made on single crystals of uracil-beta-D-arabinofuranoside, which were irradiated by 4-0 MeV electrons at 77 K. At low temperatures, two radicals have been identified, one attributed to a hydrogen abstraction from 05' in the sugar moiety and the other to a radical anion located on the pyrimidine ring. The former is very unstable and seems to act as a precursor to other unidentified radical species stable at 77K. At room temperature, the main resonance is due to hydrogen addition to C5 and is probably produced by protonation of the anion. This same radical is also produced by X-irradiation at room temperature.     

Cyanide inhibition of cytochrome c oxidase. A rapid-freeze e.p.r. investigation.

The inhibition of cytochrome c oxidase by cyanide, starting either with the resting or the pulsed enzyme, was studied by rapid-freeze quenching followed by quantitative e.p.r. It is found that a partial reduction of cytochrome oxidase by transfer of 2 electron equivalents from ferrocytochrome c to cytochrome a and CuA will induce a transition from a closed to an open enzyme conformation, rendering the cytochrome a3-CuB site accessible for cyanide binding, possibly as a bridging ligand. A heterogeneity in the enzyme is observed in that an e.p.r. signal from the cytochrome a3 3+-HCN complex is only found in 20% of the molecules, whereas the remaining cyanide-bound a3-CuB sites are e.p.r.-silent.     

Aspects of audit. 1. The background.

Methods of reviewing health care already exist in Britain, but the debate continues about how practical and acceptable such a review is. The many different terms used to describe review only confuse the issue. "Audit" is a useful term for describing the review of medical work by medical people. This can be divided into "internal audit," or peer review, and "external audit"--that is, review by organisations outside hospital and general practice. The concepts of internal and external audit have a great impact upon the attitudes held by the medical profession about audit. The shortcomings of audit by the professional standards review organisations in the United States are not inevitable in Britian.     

Neurobiology of Stomotoca. I. Action systems.

The layout of nerves, muscles, and conducting epithelia is described for the simple hydrozoan medusa Stomotoca. Comparisons are drawn with Sarsia and other recently studied forms. The major action systems are those responsible for swimming, crumpling (protective involution), tentacle posture, pointing (unilateral reciprocal flexions of the manubrium and margin), and visceral movements (barely mentioned). Crumpling is a simple summating response in this species. Crumpling and pointing are considered to use the same effectors but different conduction pathways. New histological results include the demonstration of a nerve plexus running through the endodermal canal system and a nerve plexus in the ectoderm encircling the peduncle. Special attention is given to the distribution of synapses and gap junctions, as possible trasmission pathways in behavioral responses. Some details are included on organization within the marginal nerve rings.     

Thermodynamics of cell adhesion. II. Freely mobile repellers.

The equilibrium adhesion of a cell or vesicle to a substrate is analyzed in a theoretical model in which two types of mobile molecules in the cell membrane are of interest: receptors that can form bonds with fixed ligands in the substrate and repellers that repel the substrate. If the repulsion between the repeller molecule and substrate is greater than kT, there is substantial redistribution of the repellers from the contact area. Coexisting equilibrium states are observed having comparable free energies (a) with unstretched bonds and repeller redistribution and (b) with stretched bonds and partial redistribution.     

Crystal structure and n.m.r. analysis of lactulose trihydrate.

The 13C CPMAS n.m.r. spectrum of 4-O-beta-D-galactopyranosyl-D-fructose (lactulose) trihydrate, C12H22O11.3 H2O, identifies the isomer in the crystals as the beta-furanose. This is confirmed by a crystal structure analysis, using CuK alpha X-ray data at room temperature. The space group is P212121, with Z = 4 and cell dimensions a = 9.6251(3), b = 12.8096(3), c = 17.7563(4) A. The structure was refined to R = 0.031 and Rw 0.025 for 1929 observed structure amplitudes. All the hydrogen atoms were unambigously located on difference syntheses. The conformation of the pyranose ring is the normal 4C1 chair and that of the furanose ring is 4T3. The 1----4 linkage torsion angles are O-5'-C-1'-O-1'-C-4 = 79.9(2) degrees and C-1'-O-1'-C-4-C-5 = -170.3(2) degrees. All hydroxyls, ring and glycosidic oxygens, and water molecules are involved in the hydrogen bonding, which consists of infinite chains linked together by water molecules to form a three-dimensional network. There is a three-centered intramolecular, interresidue hydrogen bond from O-3-H to O-5' and O-6'. The n.m.r. spectrum of the amorphous, dehydrated trihydrate suggests the occurrence of a solid-state reaction forming the same isomeric mixture as was observed in crystalline anhydrous lactulose, although the mutarotation of the trihydrate when dissolved in Me2SO is very slow.     

Analysis of family resemblance. IV. Operational characteristics of segregation analysis.

In simulated data, segregation analysis of quantitative traits was found to be powerful for resolving a major locus from polygenic and cultural inheritance. It is reasonably robust against a variety of deviations from the model if and only if a major locus, polygenic heritability, and environment common to sibs are simultaneously included in the model, and heterogeneity tests among mating types are performed. Most of the information in quantitative data about a major locus is lost when reduced to affection status.     

Microhydrodynamics simulation of protein crystallization. I. Static calculations.

A computer simulation method is proposed to study the effects of hydrodynamic interactions on protein crystallization. It is a combination of Stokesian dynamics and continuum hydrodynamics and is referred to as "microhydrodynamics." The method is checked against analytical expressions for Stokes drag and diffusion coefficients for unit spheres. For a number of protein molecules the diffusion coefficients have been calculated and compared with experimental values. It is shown that the method works well for stationary calculations. Using dynamical calculations interacting protein molecules will be simulated to study the events in the early stages of protein crystallization.     

Brachyptera Group. Sp.32. C. Brachyptera. Sp.33. C.c RUFA. Sp.34. C. Troglodytes. Sp.35. C. Fulvicapilla.

A part from considerations as to where it is best wedged into the linear sequence, the brachyptera group is defined in general terms as a compact group of four small or very small species which resemble one another in many important specific characters and the other thirty-six species classified here as Cisticola in so many ways of form, coloration and behaviour as to make them best understood by classifying them also under that generic name.     

Antigenic determinants of adenovirus capsids. I. Measurement of antibody cross-reactivity.

Evidence is presented that the type-specific antibody to the adenovirus hexon is not simply the antibody with the highest activity for cross-reactive determinants, but is a distinct, minority population that recognizes seperate determinants. To quantify it, we have developed an inhibition method with radio-immunoprecipitation (RIP) as a sensitive assay for the type-specific antibody that remains after all the excess of cross-reactive antibody has been blocked by heterologous antigen. During the primary response, 0.1 to 1% of antibody to types 2 or 5 hexon is type-specific, but after boosting, this population may reach 10 to 20%. Antibody to fiber is more than 70% type-specific during primary and secondary responses. The cross-reacting antibody can be removed on immunoabsorbent columns without affecting the virus neutralization titer of the serum.     

Neurobiology of Stomotoca. II. Pacemakers and conduction pathways.

Evidence is presented for separate conduction pathways for swimming and for tentacle coordination in the marginal nerves of the jellyfish Stomotoca. The effector muscles are fired through junctions sensitive to excess Mg++, probably represented by the neuromuscular synapses observed by electron microscopy. The swimming effector (striated muscle) fires one-to-one with nerve input signals and myoid conduction occurs. Tentacle responses (smooth muscle contractions) involve facilitation, presumably at the neuro-effector junction; responses are graded and nonpropagating. Electrical correlates of two further conducting systems using the marginal nerves have been recorded. Their functions are unknown. One, the bridge system, extends up the four radii and encircles the peduncle; the other (ring system) is confined to the margin. A fifth conducting system is inferred in the case of the pointing response and its distribution is plotted. Signals have not been obtained from it. Pointing is accompanied by a burst of muscle potentials in the radial smooth muscles and is exhibited after a lengthy latency, indicating a local pacemaker. A sixth conducting pathway is the epithelial system, which mediates crumpling, a response involving the radial muscles without pacemaker intervention. Characteristic conduction velocities and wave forms are noted for the first four systems and for epithelial pulses. All systems, except perhaps the pointing conduction system, through-conduct under excess Mg++. Spontaneous activity patterns are described for the swimming, tentacle pulse, and ring systems. Abrupt increases in light intensity inhibit spontaneous activity, sudden decreases augmenting it. In the absence of specialized photoreceptors, light is presumed to act directly on central neurons. Epithelial pulses inhibit swimming, apparently by blocking the generation or conduction of the primary nervous events. This observation, taken in conjunction with evidence of feedback inhibition of the primary swimming system by the cells it fires, is discussed in relation to possible mechanisms whereby the output of nerve cells might be altered by activity in the excitable epithelial cells which envelop them.     

Actions of the A.M.A. House of Delegates

This summary from the Executive Vice-President's office of the American Medical Association covers only a few of the many important subjects dealt with by the House and is not intended as a detailed report on all actions taken.     

Theodoropoulos, D.I. Invasion biology. Critique of a pseudoscience.

The back cover of this book states that ‘contrary to theclaims of the nativists, research shows that man-dispersed speciesincrease biological diversity, benefit ecosystems, and act asan important force for healing the planet’. This is anuncompromising statement, and David Theodoropoulos divides hisdevelopment of the arguments supporting this statement intothree parts. Part I (Chapters 1–6) is ‘Nature, Dispersaland Reaction’. Part II (Chapters 7 and 8) is ‘Why?Psychology, Politics and Pseudoscience’. Part III (Chapters9–11) is ‘Humanity and Diversity’. There isalso an ‘Introduction’ including a summary of findingsand ‘An outline for a new theory of anthropogenic dispersal’,     

The genetics of self-incompatibility in Brassica campestris L. ssp. Oleifera Metzg. I. Characteristics of S-locus. Control of self-incompatibility

Self-incompatibility in Brassica campestris c.v. Arlo is controlled by a single locus sporophytic system. The identity and expression of the S alleles were determined in eight inbred and two hybrid families. It was found that co-dominance of alleles is more frequent in the stigma, whereas dominance relations between pairs of alleles predominate in the pollen. A linear order of dominance was established between six S alleles and alleles high, intermediate and low in the dominance series were recognized.In considering the variation in the expression of compatibility and the segregation ratios in inbred, F₁, F₂ and backcross progenies, the presence of a specific S allele conditioning self-fertility, or a single dominant self-compatibility factor independent of the S locus could not be established. Instead, self-compatibility in this cultivar was ascribed to the segregation of a polygenic complex which is capable of modifying the incompatibility reaction to the point of self-fertility, or to a reduction in the strength of the reaction due to the presence of S alleles low in the dominance series.     

Actions of the A.M.A. House of Delegates

This skimming and skipping report on the proceedings of the House of Delegates of the American Medical Association at the Atlantic City meeting covers only a few of the many important subjects dealt with by the House and is not intended as a detailed report on all actions taken.     

Modeling the electrophoresis of lysozyme. II. Inclusion of ion relaxation.

In this work, boundary element methods are used to model the electrophoretic mobility of lysozyme over the pH range 2-6. The model treats the protein as a rigid body of arbitrary shape and charge distribution derived from the crystal structure. Extending earlier studies, the present work treats the equilibrium electrostatic potential at the level of the full Poisson-Boltzmann (PB) equation and accounts for ion relaxation. This is achieved by solving simultaneously the Poisson, ion transport, and Navier-Stokes equations by an iterative boundary element procedure. Treating the equilibrium electrostatics at the level of the full rather than the linear PB equation, but leaving relaxation out, does improve agreement between experimental and simulated mobilities, including ion relaxation improves it even more. The effects of nonlinear electrostatics and ion relaxation are greatest at low pH, where the net charge on lysozyme is greatest. In the absence of relaxation, a linear dependence of mobility and average polyion surface potential, (lambda zero)s, is observed, and the mobility is well described by the equation [formula: see text] where epsilon 0 is the dielectric constant of the solvent, and eta is the solvent viscosity. This breaks down, however, when ion relaxation is included and the mobility is less than predicted by the above equation. Whether or not ion relaxation is included, the mobility is found to be fairly insensitive to the charge distribution within the lysozyme model or the internal dielectric constant.     

A novel oligoribonuclease of Escherichia coli. II. Mechanism of action.

Detailed studies of the mechanism of action of the novel oligoribonuclease of Escherichia coli described in the previous paper (1) led to the following conclusions. 1. The enzyme prefers a free 3'-hydroxyl group for its action. 2. The enzyme attacks the oligoribonucleotide substrate in a sequential manner from the 3' end producing 5'-ribonucleotides. 3. The mode of attack appears to be processive; the enzyme acts by degrading one oligoribonucleotide chain to completion before proceeding to the hydrolysis of another chain. 4. The reaction rate is inversely proportional to the chain length of the substrate; however, the enzyme has a higher affinity for longer chains. 5. The enzyme activity is markedly inhibited by secondary structure; oligoribonucleotides combined with complementary polyribonucleotides are attacked poorly below the melting temperature of the complex and efficiently above the melting temperature. 6. The enzyme is inhibited by 5'-nucleotides of adenine and guanine; those of cytosine and uracil have a much smaller effect. The enzyme is not inhibited by 3'-nucleotides. 7. Studies with dinucleoside monophosphate show highest reaction rates with pyrimidine sequences in the order: CpCgreater than UpUgreater than CpUgreater than UpC. The presence of guanine at the 3' end is strongly inhibitory, and reaction rates are CpGgreater than UpG=ApGgreater than GpG.     

Bend propagation in flagella. I. Derivation of equations of motion and their simulation.

A set of nonlinear differential equations describing flagellar motion in an external viscous medium is derived. Because of the local nature of these equations and the use of a Crank-Nicolson-type forward time step, which is stable for large deltat, numerical solution of these equations on a digital computer is relatively fast. Stable bend initiation and propagation, without internal viscous resistance, is demonstrated for a flagellum containing a linear elastic bending resistance and an elastic shear resistance that depends on sliding. The elastic shear resistance is derived from a plausible structural model of the radial link system. The active shear force for the dynein system is specified by a history-dependent functional of curvature characterized by the parameters m0, a proportionality constant between the maximum active shear moment and curvature, and tau, a relaxation time which essentially determines the delay between curvature and active moment.     

Magnesium-induced self-association of calf brain tubulin. I. Stoichiometry.

The self-association of calf brain tubulin at pH 7.0 in the presence of magnesium ions has been examined by velocity sedimentation. The schlieren patterns were analyzed by methods described by Gilbert and by Cox. The observed process is best described in terms of a rapidly reversible progressive self-association of the tubulin dimer with identical chain elongation equilibrium constants, k, terminated by a ring-closing step, at degree of polymerization n = 26 +/- 2, with k26 greater than k. The end product of the polymerization reaction has a sedimentation coefficient s20,w0 k2 +/- 2 S. It is hydrodynamically equivalent to a closed ring structure observed in the electron microscope at identical conditions.