National Academy of Sciences Annual Meeting Source: Proceedings of the National Academy of Sciences of the United States of America, Vol. 63, No. 1 (May 15, 1969), pp. 219-232 Published by: National Academy of Sciences Stable URL: http://www.jstor.org/stable/59243 . Accessed: 07/05/2014 14:19 Your use of the JSTOR archive indicates your acceptance of the Terms & Conditions of Use, available at . http://www.jstor.org/page/info/about/policies/terms.jsp . JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact [email protected]. . National Academy of Sciences is collaborating with JSTOR to digitize, preserve and extend access to Proceedings of the National Academy of Sciences of the United States of America. http://www.jstor.org This content downloaded from 169.229.32.136 on Wed, 7 May 2014 14:19:28 PM All use subject to JSTOR Terms and Conditions
Transcript
National Academy of Sciences Annual MeetingSource: Proceedings of the National Academy of Sciences of the United States of America,Vol. 63, No. 1 (May 15, 1969), pp. 219-232Published by: National Academy of SciencesStable URL: http://www.jstor.org/stable/59243 .
Accessed: 07/05/2014 14:19
Your use of the JSTOR archive indicates your acceptance of the Terms & Conditions of Use, available at .http://www.jstor.org/page/info/about/policies/terms.jsp
.JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range ofcontent in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new formsof scholarship. For more information about JSTOR, please contact [email protected].
.
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The National Academy of Sciences held its 106th Annual Meeting in Washington, D.C., on April 28-30, 1969. Academy Awards were pre- sented on Monday evening. The Academy Dinner on Tuesday evening was highlighted by an address by Lee A. DuBridge, Special Assistant to the President for Science and Tech:nology. Four symposia and three groups of contributed papers comprised the scientific sessions. Abstracts of contributed papers are printed in this issue.
PRESENTATION OF ACADEMY AWARDS
Henryk Arctowski Award
J. PAUL WILD, Commonwealth Scientific and Industrial Research Organi- zation, Australia
EUGENE NEWMAN PARKER, University of Chicago
U.S. Steel Foundation Award in Molecular Biology
WILLIAM BARRY WOOD III, California Institute of Technology
Alexander Agassiz Medal
FREDERICK C. FUGLISTER, Woods Hole Oceanographic Institution
James Craig Watson Medal
JtRGEN KURT MOSER, New York Uniiversity
219
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College of Physicians and Surgeons New York, New York
RUPERT E BILLINGHAM, University of Pennsylvania School of Medicin-e, Philadelphia, Pennsylvania: Genetical and Immunological Considerations Essential to the Under- standing of the Biological Problems Related to Homo- and Heterotransplantation.
'RITZ H. BACH, University of Wisconsin School of Medicine, Madison, Wisconsinl: Biological Methods for the Study of Genetico-, Immuno-, and Histocompatibility, and Various Therapeutic kResources Applicable to the Suppression or Control of Immunologi- cal Responses.
JOHN P. MERRILL, Peter Bent Brigham Hospital, Boston, Massachusetts: Experience with and Lessons from Transplantation of a Paired Organ, the Kidney.
NORMANE. STUJMWAY, Stanford University School of Medicine, Palo Alto, California: Experimental and Clinical Aspects of Transplantation of an "Unpaired" Organ, the Heart.
V'INCENT P. DOLE, Rockefeller University Hospital, New York, New York: Ethical Aspects and Sociological Implications of Organ Transplantation as a Therapeutic Procedure.
Monday Afternoon:
SYMPOSIUM ON PLASMA LIPOPROTEINS
Chairman: DONALD S. FREDRICKSON
J-oH L. ONCLEY and NANCY R. HARVIE, University of Michigan, Ann Arbor, Michigan: Lipoproteins-A Current Perspective of Methods and Concepts.
ANTONIO M. GOTTO, JR., National Heart Institute, Bethesda, Maryland: The Structure of Plasma Lipoproteins.
ALEXAND-IER V. NICHOLS, University of California and Lawrence Radiation Laboratory, Berkeley, California: Functions and Interrelationship of Different Classes of Plasma Lipoproteins.
DONALD S. FREDRICKSON, National Heart Institute, Bethesda, Maryland: Application of Plasma Lipoproteins to the Study of Hluman Mutants and Disease.
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Abstracts of Papers Presented at the Annual Meeting, Washington, D. C., 28-30 April 1969
The Effect of Protoplasmic Acidity and of Light on the Bioelectric Potential of Valonia and Boergesenia
Valonia and Boergesenia normally display a small potential difference of 10 to 20 mv across the protoplasm, the vacuole being positive to the sea water. This is only slightly increased by illumination, or by the raising of the pH of the sea water, if the latter is free from ammonia. However, the addi- tion of 10-4 to 10-3 M NH4Cl increases the potential difference, the increase being further promoted by raising the pH, and even more rapidly in turn by light (100 mc). A potential difference of +50 to +60 mv can be so produced. Light presumably further decreases the acidity outside the cell by fixing CO2 and permits more undissociated ammonia to penetrate the cell. There are very large light and dark transients.
The effect of the ammonia (or of the increased pH resulting from it within the cytoplasm) seems in turn to be due to its influence on the plasmalemma, increasing the mobility of K ion in the latter. The pH, ammonia, and light effects are almost completely abolished in K-free sea water, but markedly enhanced by increased KCI. A poten- tial difference of more than +100 mv has been observed in Boergesenia ex- posed to a combination of light, high pH, amimonia, and increased KCl (0.05 M).
Opposite effects are produced by penetrating weak acids or by inhibitors which presumably increase proto- plasmic acidity. When the sea water
is bubbled with 5 per cent CO2 in air, prompt reversal of the po- tential difference to -5 or -10 mv is usually brought about. Light over- comes this, but in subsequent dark periods the potential difference may increase to -20 or -30 mv, usually after complicated transients with 2 or more cusps. A still greater negative potential difference (up to -90 ma) is produced by low concentrations of cyanide, azide, or dinitrophenol, pre- sumably by the production of organic acids in fermentation. Light over- comes the effect of these agents by C02 fixation, increase of the external pH, and decrease of the penetration of the inhibitors, which are weak acids. Anoxia also produces a small negative potential difference, presumably again by fermentation; it is light-reversible as well. Although the potassium .mobility is often decreased by these treatments, it is probably not responsi- lble for the large reversals. It seems imore likely that there is an effect upon the tonoplast by the protoplasmic acidity, which leaves the plasmalemma potential more or less unchanged.
LAWRENCE R. BLINKS
Hopkins Marine Station of Stanford University
lJncertainties in Tests of Long- ]Range Charge Independence
Usual comparisons of the pion- nucleon coupling constant g obtained from distant collisions in proton-proton (p-p) and neutron-proton (n-p) scatter-
223
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224 N. A. S. ANNUAL1 MIEETING 196(N) Pc-. N. A. S.
ing employing pseudoscalar couplinLg theory do not consider nucleon-nucleon (N-N) pair formation in the pion's vicinity sufficiently. Vector mesons (co,p) provide N-N interactions leading (Breit, G., Proceedings of the Inter- national Conference on Nucleon Struc- ture, Stanford University, 1963, ed. R. Hofstadter and L. I. Schiff (Stanford, California: Stanford Univ. Press), to a pion picture similar to that of Fermi and Yang (Phys. Rev., 76, 1739 (1949)) without the questionable "weak" type N-N coupling. Absorp- tion of physical pions by nucleons is not expected therefore to be purely pseudoscalar even if this should apply to bare pions. Universal presence of factor (mr/IM)2 characteristic of pseu- doscalar one-pion exchange (OPE) phase-shift formula (mr, M for pion, nucleon masses) is thus questionable for actual OPE effects. This factor is 6.7 per cent larger for r+ and wr- than for w ?. Further, (a) employment of measured pion masses is justifiable for physical rather than bare pions, (b) the OPE potential depends on m7, expo- nientially, (c) p-p and n-p interactions depend on charged and neutral pions differently. Therefore, precision tests of isotropy of basic symmetry of r-N interaction in isotopic spin space by N-N and N-N scattering should con- sider admixtures of other than pseudo- scalar pion-physical-nucleon couplings. Some empirical differences (Breit, G., Rev. Mod. Phys., 39, 560 (1967); Seamon, R. E., K. A. Friedman, G. Breit, R. D. Haracz, J. lYf. Holt, and A. Prakash, Phys. Rev., 165, 1579 (1968)) in effective g's for physical pions on physical nucleons have right order to fit reasonable admixtures of interactions with OPE potential free of (m7r/M) 2. Better knowledge of corrections for isobar formation and of two-pion, vector meson and eta ex- changes is needed to ascertain the admixtures reliably.
Supported by the Atomic ELner-gy Commission (NYO-4022-3).
G. BREIT
State University of New York at Buffalo
Energy and Anesthetic-Responsive Regions of Mitochondrial Membranes
The possibility of probing hydro- phobic regions of membranes with 8- anilino-1-naphthalene sulfonate (ANS) (Weber, G., and D. R. Laurence, Biochem. J., 56, 31-P (1956)) has recently beeni realized (Azzi, A., B. Chance, G. K. Radda, and C. P. Lee, N. A. S. PROCEEDINGS, 62, no. 2 (1969); Chance, B., A. Azzi, L. lMfela, G. K. Radda, and H. Vainio, FEBS Letters, in press; Tasaki, I., A. Watanabe, R. Sandlin, and L. Carnay, N. A. S. PROCEEDINGS, 61, 883 (1968); Vander- kooi, J., and T. MAlartonosi, Biophys. Soc. Abstr., A-235 (1969)); two activ- ity-related membrane transitions are now resolvable by kinetic studies. A fast-flow fluorometer (Chance, B., anid lMf. Pring, Mosbach Coll., 19, 102 (1968)) reads out fluorescence changes of membranes from 2 msec onward, with excitation at 405/366 nm and emission at 530-510 nm. Protein con- centrations of 30 ,ug/ml are adequate.
(1) MViembrane fragments that show energy coupling reactions exhibit two types of ANS environment: one in- volves a region of the membrane oc- cupiable by a large number of loosely bound ANS molecules (>200 nmoles/ mg pr) that react rapidly (--350 sec1), the other by a smaller number of tightly bound ANS molecules (<10 nmoles/mg pr) that react slowly (0.2 sec1). Both regions shown similar
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fluorescence depolarization. The slow region enhances ANS fluorescence only when the membrane is energized by ATP or by electron flow from substrate to oxygen; at low [ANS] (<50 ,uM), membrane energization causes a dou- bling of ANS fluorescence at a similar rate (N. A. S. PROCEEDINGS, 62, no. 2 (1969)). Thus, the change of state of the membrane identified by the fluo- resence probe technique is here shown to involve a structural reorganization with a 0.2 sec-1 rate constant. This readily reversible structural alteration occurs in membrane fragments that are not osmotically responsive and do not show matrix space reorganization, as in the case of intact mitochondria studied by Hackenbrock (N. A. S. PROCEED- INGS, 61, 598 (1968)).
(2) Structural reorganization is ob- served when local anesthetics such as butacaine accelerate eniergy-dependent calcium uptake in intact mitochondria (Mela, B., Biochemistry, in press). ANS labeling of these membranes shows approximately doubled fluores- cence caused by butacaine addition (--100 MM). Kinetic studies again show two types of ANS binding: one with a first-order constant in excess of 350 sec-1 and the other with a constant of approximately 2.0 sec-1. Both fast and slow reactions involve regions of the inembrane with similar ANS affinities and fluorescence depolariza- tion. Thus, low butacaine concentra- tions induce a first-order transition between membrane states of high and low calcium transport activity. These two activity-related structural changes reported by ANS in mitochondrial membranes are found to lie in the time region 0.2 to 2.0 sec-1.
B. CHANCE, C. P. LEE L. MELA, A. Azzi
C. K. RADDA
University of Pennsylvania
Electrical Analogues for Tissues
The equations of Maxwell and Ray- leigh for the electrical resistance of suspensions of spheres and cylinders have been widely used to calculate the volume concentration of non- conducting cells in several tissues. The assumptions made in the derivations of these equations are not valid over at least part of the concentration range from 50 to 100 per cent, so that such calculations are without analytical basis.
Approximations for uniform, uni- formly separated, space-filling figures and for randomly oriented, uniform, and uniformly distributed conducting planes showed that each of the equa- tions was correct for volume concentra- tions approaching 100 per cent.
Analogue measurements were made with conducting paper for circular cylinders in square and hexagonal arrays and with an electrolytic tank for spheres in simple and face centered cubic arrays. The available theories are not entirely satisfactory.
Similar analogue measurements were nade for a square array of square c ylinders and a hexagonal array of hexagonal cylinders and for a cubic array of cubes and a hexagonal array of tetra-kai decahedra. In all cases it was found that the measured volume concentrations agreed with those given by the simple Rayleigh and Maxwell equations, to within the experimental accuracies of about 1 per cent, over all the concentration ranges measured from 30 per cent or less to 90 per cent or more. These analogue calculations thus provide a basis for the use of the equations over the entire range.
KENNETH S. COLE CHoH-LuH LI
ANTHONY F. BAK
NVational Institutes of Health
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The Relation of the Inhibitory and the Misreading Effects of Streptomycin on Ribosomes
The mechanism by which strepto- mycin inhibits ribosomes has been more obscure than its misreading effect, which evidently involves distortion of the recognition region. Using phage MS2 RNA as messenger in E. coli extracts, we have found that strepto- mycin immediately blocks polypeptide chain extension (N. A. S. PROCEEDINGS, 61, 1279 (1968)). However, the re- sulting stabilization of the polysomes, in contrast to that produced by various other inhibitors of the ribosome, is only transient: nascent polypeptide and messenger slowly fall off the ribosome, with a half time of about four minutes at 34?. During the transient stabiliza- tion the nascent polypeptides appear to be in the P site, since they are all rapidly released by puromycin; and their eventual release by streptomycin evidently requires transfer to the A site, since this release is halted by drugs that block the transfer either directly (chloramphenicol) or by interfering with aminoacyl-tRNA binding in the A site (tetracycline). These observa- tions may be explained if streptomycin distorts the A site in a way that (a) hinders the binding of aminoacyl- tRNA (or at least its binding in a position where it can accept peptidyl transfer), and (b) weakens retention of the peptidyl-tRNA formed in the A site by this transfer. Thus the in- hibitory action of streptomycin may well be due to distortion of the same region that is responsible, under other circumstances, for misreading.
BERNARD D. DAVIS JUAN MODOLELL
iharvard Medical School
Tricarbonates Derived from t-Butyl Alcohol and t-Butyl Mercaptan
After studies on the preparation of carbonic-phosphoric anhydrides (cf. Tarbell, D. S., and M. A. Insalaco, N. A. S. PROCEEDINGS, 57, 233 (1967)), we found that treatment of sodium t- butyl thiolcarbonate with phosgene yielded the crystalline tricarbonate I, RSCOOCOOCOSR, which decomposed on heating to the dicarbonate II, RSCOOCOSR, and this in turn to the monocarbonate III, RSCOSR, each with the loss of carbon dioxide (R = (CH3)3C) (Friederang, A. W., and D. S. Tarbell, Tetrahedron Letters, 5535 (1968)). We now find that the corre- sponding oxygen tricarbonate IV, ROCOOCOOCOOR, can be obtained as a crystalline solid, m.p. 64.5-65?, by treatment of potassium t-butoxide, (CH3)3COK, with carbon dioxide, fol- lowed by phosgene; IV yields 3 moles of carbon dioxide, 1 mole of isobutene, and 1 mole of t-butyl alcohol, when heated without solvent above the melting point. The dicarbonate, ROCOOCOOR (Howe, J. H., and L. R. Morris, J. Org. Chem., 27, 1901 (1962)), is an intermediate in this de- composition. The tricarbonates I and IV appear to be the first examples of their class, and their chemistry will be discussed.
CHRISTOPHER S. DEAN D. STANLEY TARBELL
Vanderbilt University
Geometric Programming, Chemical Equilibrium, and the Antientropy Function
The culmination of this paper is the following duality principle of thermo- dynamics
maximum S = minimum S*. (1)
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The left side of (1) is the classical characterization of equilibrium. It says to maximize the entropy function S with respect to extensive variables which are subject to certain con- straints. The right side of (1) is a new characterization of equilibrium and concerns minimization of an anti- entropy function S* with respect to intensive variables. Relation (1) is applied to the chemical equilibrium of a mixture of gases at constant tem- perature and volume. Then (1) spe- cializes to
minimum F = maximum F*, (2) where F is the Helmholtz function for free energy and F* is an anti-Helm- holtz function. It results that the right side of (2) is an unconstrained maximization problem and gives a simplified practical procedure for ca]cu- lating equilibrium concentrations. We also give a direct proof of (2) by the duality theorem of geometric pro- gramming. The duality theorem of geometric programming states that minimum cost = maximum anticost.
(3) We complete this circle of ideas by exhibiting ani intimate relation between geometric programming and the Dar- win-Fowler method in statistical ther- modynamics.
R. J. DUFFIN C. ZENER
Carnegie-Melton University
The Role of Ecdysone and Neurosecretion in Puparium Formation (Pupariation) of Flies
During pupariatioii fly larvae first contract to form the barrel-shaped puparium, anid then the cuticle darkens and hardens by phenolic tanning. That tanniing which one of us (G. F.)
demonstrated 35 years ago is induced by a hormone (known as ecdysone): Larvae of Calliphora erythrocephala were ligated into two parts before a critical period. The hind parts which would remain untanned were induced to tan by the injectioni of blood from pu- pariating larvae. The validity of this experiment has recently been ques- tioned by Ohtaki et al. (Biol. Bull., 135, 322 (1968)) who failed to re- produce it with the use of a member of a different family (Sarcophaga peregrina) and a different technique. On reinvestigation, the original results were readily reproduced with Phormia regina, but not with Sarcophaga bul- lata. The following observations pos- sibly explain these conflicting data. When larvae of S. butdata are ligatured after the critical period, injection of brain extracts into the hind parts greatly accelerates pupariation. The following preparations have the same effect: Extracts from pars intercere- bralis, or from corpora cardicaca from fly larvae, Periplaneta, or Pyrrhocoris. Injection of additional ecdysone does n-ot have this effect. Thus the active material is neurosecretory and does not act via releasing ecdysone from the ring gland. These data suggest that (qualitative or quantitative effects of ecdysone cannot be gauged without a consideration of neurosecretory activ- ilty. The active factor is different from bLursicon, but it may be identical with the ("activating") brain hormone.
G. FRAENKEL JAN ZDAREK
University of IlliTnois
The Function of C-Terminal Tyrosine Residues in Aldolases
The C-terminal tyrosille residues in rabbit muscle aldolase have previously been shown to be essential for full
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activity with fructose-1,6-P (FDP) but not for activity with fructose 1-P (FIP), suggesting that these tyrosine residues play a role in the recognition of the 6-phosphate group. We have now shown that the presence of sub- strate or substrate analogues, such as hexitol diphosphate, renders these tyrosine residues resistant to the action of carboxypeptidase. Reciprocal ef- fects can also be demonstrated for the interaction of the enzyme with alde- hyde phosphate substrates such as glyceraldehyde 3-P or erythrose 4-P. The native enzyme is inactivated by the latter substrate, with the incorporation of one equivalent per active site. The inactivated enzyme, which contains bound phosphate, is resistant to car- boxypeptidase. After tyrosine has been removed from the native enzyme, the enzyme is no longer inactivated by glyceraldehyde 3-P. The rabbit liver enzyme is not inactivated by glycer- aldehyde 3-P, nor does it show en- hanced activity with FDP (as com- pared with FIP). We have now shown that the C-terminal residues in the rabbit liver enzyme are glycine, rather than tyrosine. In the case of aldolase from spinach leaves, C-termi- nal tyrosines are present and are essential for activity with FDP. The kinetics of inactivation by carboxy- peptidase suggest that interaction be- tween the subunits plays a role in maintaining the catalytic activity.
B. L. HORECKER, R. GRACY A. LACKO, L. DAVIS
R. ADELMAN
Albert Einstein College of Mlledicine
Mechanisms of Hormonal Regulation of Enzyme Synthesis
Synthesis of the enizyme, tyrosinle-a- ketoglutarate transaminase, is acceler-
ated by both steroid (hydrocortisone) and polypeptide (glucagon) hormones in cultures of Reuber (H35) hepatoma cells. The two hormones together yield additive or synergistic effects. Label and chase experiments show that the enzyme undergoes turnover in these cells with a half life of about three hours, and measurements of the decline in enzyme synthesis after actinomycin indicate that the trans- aminase mRNA decays at about the same rate. With these data it was possible to show that iniduction by hydrocortisone involves production of a substance with a lifetime like that of the transaminase mRNA, while glucagon induction does not. Sec- ondly, induction by hydrocortisone is completely sensitive to actinomycin, whereas glucagon induction is insensi- tive for a period of time corresponding to the lifetime of the transaminase mRNA. Finally, preinduction with hydrocortisone removes a limitation in the response to glucagon; the latter hormone effects a very rapid and large induction which is insensitive to actino- mycin in cells pretreated with hydro- cortisone. Preinduction with glucagon does not alter the response to hydro- cortisone. We conclude that the steroid hormone acts on genetic tran- scription to promote synthesis of transaminase-specific messenger RNA, while glucagon acts at some post- transcriptional step in enzyme syn- thesis.
FRANcIs T. KENNEY, KkI-LIN L,EE JERRY R. REEL
Oak Ridge National Laboratory
The Conductivity of Strong Electrolytes at Finite Dilution
The electrostatic forces between the ions in an electrolyte affect their
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migration velocities by two miecha- nisms: A distortion of the shielding charge cloud around each ionl produces a field which usually retards its inotioin, and the force of an electric field on the charge cloud, transmitted to the sol- vent, produces a countercurrent. In first approximation the effects are proportional to the square root Cl/2 of the concentration; the appropriate coefficients were computed long since. Second-order terms are proportional to Cli2 log C; again with predictable coefficients, these have been computed for arbitrary mixtures of ions. Pre- vious computations for simple binary electrolytes were found incomplete. To be specific, a term El arises from a more accurate computation of the charge asymmetry caused by migration, and a term E2 from a modification of the charge asymmetry by hydro- dynamic flow. Both remain un- changed, but an effect reciprocal to the latter produces a significant term E3. In the simplest case the two cross- terms are equal; in general, E2 and E3 are reciprocal in the sense of irreversi- ble thermodynamics.
LARS ONSAGER MOU-SHAN CHEN
Yale University
Regeneration of Oxidative Phosphorylation in Aged Mitochondria by Prostaglandin B1
Studies on humans subjected to physical or psychic stress revealed common plasma increments in the level of phosphatidyl glycerol. Similar changes were found in the plasma and tissues of acceleration-stressed rats. The effectls of acceleration on the plasma level of phosphatidyl glycerol
could be epIro(luced by the injection of prostaglandin E)j. Experiments in vivo showed exceptionally fast turinover rates of P32 in phosphatidyl glycerol isolated from liver mitochondria of rats. These observations led to studies on the possible role of prostaglandins and phosphatidyl glycerol in phos- phorylation mechanisms. When aged mitochondria were further "un- coupled" with Triton X-100 and re- acted with adenosine diphosphate and p32 under conditions for oxidative phosphorylation, analysis of the re- action products by ion exchange chro- matography gave increased levels of adenylic acid and inorganic phosphate. Addition of prostaglandin E1 and phosphatidyl glycerol to the reaction reversed the dephosphorylation and yielded a net increase in adenosine triphosphate correlated with a decrease in inorganic phosphate. In the pres- ence of Tritoni X-100, both prosta- glandin E1 and prostaglandin B1 were equally effective in reactivating phos- phorylation. In the absence of Triton X-100, prostaglandin El was inactive, 'but prostaglandin B1 was effective alone. Thin-layer chromatography on silica of the one-minute reaction prod- ucts extracted by chloroform-methanol separated a radioactive phosphate- labeled lipid component derived pre- sumptively from prostaglandin Bl.
The implication of prostaglandin B1 as a possible intermediate in mito- chondrial phosphorylation offers a niew probe to the mechanisms involved in the transformation of oxidative energy.
B. DAVID POLIS ANNA MARIE PAKOSKEY
H. W. SHMUKLER
Alerospace Medical Research Depart- ment,
UT. S. Naval Air Development Center, Warminster, Pennsylvania
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A Polymolecular Interpretation of Growth Rates of Social Problems
Are the decreases in the social quality of our citizens evidenced by rising crime and riot rates environ- mental or hereditary? Can any quan- titative method be developed to reduce the environment-heredity-uncertainty? The proposed analysis compares the rates of growth of social problems to those of possibly relevant segments of our population. Estimated rates of growth of riots and of violent crime are, respectively, about 50 and 10 per cent a year (see Shockley, W., "Human quality problems and research taboos," in Proceedings of the 1968 Conference of the Educational Records Bureau). Two personality traits, neuroticism (emo- tional instability) and extraversion (carefreeness), are almost as heritable as intelligence (see Eysenck, H. J., in Crime and Personality (Houghton Miff- lin, 1964)), about 70 to 80 per cent of the variance in IQ under normal con- ditions being genetically controlled (Jensen, A. R., Harvard Educational Review, Winter 1968). Eysenck re- ports that neuroticism and extraver- sion are significantly high for unwed mothers and women prisoners, suggest- ing that unwed mothers can transmit genetically controlled antisocial be- havior traits. If so, the compound- interest-like rates of increase of 7 per cent a year for white illegitimate births and 3 per cent for nonwhite may be related to the 10 and 50 per cent rates for violent criine and riots: If a violent crime requires the interaction of two persons, and the nucleation of a riot 16 persons, then the rates quoted for the increase of illegitimacy would ac- cord with the growth rates of 14 per cent for white violent crime and 48 per cent for Negro riots if these social phenomena involve bringing antisocial individuals together by mechanisms
equivalent to the random collision of molecules in a chemical reaction.
W. SHOCKLEY
Stanford University
Toward a Theory of Mind
Efforts to cope with problems of mental experience in the bisected brain have led to a modified interpretation of consciousness. The current con- cept departs from prevailing materialist approaches of 20th century neuro- science in postulating that conscious phenomena play an active directive role in shaping the flow pattern of cerebral excitation. Instead of being parallelistic and noninterventionist, consciousness in the present scheme becomes an integral part of the brain process itself and an essential and potent constituent of the action. Consciousness is put to work and given a use and a reason for having been evolved. Subjective experience in this interpretation is conceived to be an emergent dynamic property of cerebral excitation, inseparable from the ma- terial brain process, but different from, and more than, the collected sum of of the physicochemical components. Compared to the elementary physi- ological properties, the conscious prop- erties are more molar; they encompass and transcend the details of nerve im- pulse action in the same sense that cellular properties transcend the mo- lecular, the molecular transcend the atomic, etc. The mental forces do not violate or intervene in neuronal ac- tivity; however, they do supervene. The brain process must accordingly detect and react to the pattern proper- ties of its own excitations, responding to the gestalt qualities and forces of a given excitation pattern as an entity rather than to its individual excitatory elements. It follows that a full ex-
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planationi of a coInscious sequence of cerebrtal activity would not be possible solely in terms of the biochemical antd electrophysiological data; the pattern- derived qualities that constitute con- scious experience must be included.
ROGER W. SPERRY
California Institute of Technology
In vitro Action of Ecdysone
When the spermatocytes of dia- pausing silkworm pupae (Samia cyn- thia) have been removed from the testes and cultured in vitro, they show no detectable response after the addi- tion of a- or f3-ecdysone. By contrast, a rapid differentiation into sperma- tozoa takes place when an extractable, heat-labile, nondialyzable blood factor is present or is added to ecdysone-free culture medium. The "macromolec- ular factor" could not be detected in the blood of pupae during the first several months of diapause. However, it swiftly appears in the blood of ab- domens isolated from diapausing pu- pae subjected to integumentary in- jury or injected with a-ecdysone.
Unlike the "naked" spermatocytes, the cells within intact testes show no detectable response when either the macromolecular factor or ecdysone is added to the medium. But when both substances are added, the spermato- cytes within the intact testes undergo rapid differentiation into spermatozoa. Testes cultured for one hour in the presence of a-ecdysone show the de- velopmental response when rinsed and subsequently cultured in ecdysone- free medium containing the macro- molecular factor.
These observations suggest that ecdysone alters the permeability of the testicular walls to allow the macro- molecular factor to enter the testes. The macromolecular factor, as demon- strated in the cultures of "naked"
spermatocytes, then provokes the de- velopmental response. We suspect that this "permissive" mnode of action of eedysone may niot be peculiar to the testes.
CARROLL M. WILLIAMS MICHAEL P. 1KAMBYSELLIS
Harvard University
Role of Reversed Electron Transfer and Pyridine Nucleotide Redox State in the Control of Cellular Metabolism
Studies with perfused rat liver on the control of gluconeogenesis and citric acid cycle have clarified the role of the NAD redox state in metabolic regula- tion. Addition of fatty acids to livers increased the redox state of flavin and pyridine nucleotides. These changes are greatly diminished when oxidative phosphorylation is uncoupled. By analogy with studies on isolated mito- chondria, it is suggested that during fl-oxidation, the mitochondrial NAD- system is maintained more reduced as a consequence of reversed electron transfer from the highly reduced flavin pool. Gluconeogenesis from alanine is limited by the transfer of reducing equivalents from mitochondria to cy- tosol. This process is mediated by a malate H-shuttle, which is facilitated by an increased mitochondrial NADH/ NAD ratio. Thus, enhanced fatty aLcid oxidation stimulates the glycer- aldehyde dehydrogenase reaction in the direction of glucose synthesis. Simultaneous ethanol oxidation in- creases the NADH/NAD ratio in the cytosol, but it also increases the rate of NADH delivery to the respiratory chain. The further increase of the mitochondrial NADH/NAD ratio de- presses the oxalacetate concentration and inhibits citrate production. A fall of citrate, however, activates phospho- fructokinase, so that finally glucose
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production is inxhibited (lue to in- creased glycolytic activity. The roll of malate in the H-shuttle was revealed by experiments with n-butylmalonate which inhibited both ethanol oxidation and gluconeogenesis from pyruvate. These studies illustrate both the ther- modynamic control function of NAD redox systems and the kinetic control
function of ntet lhydrogeni flux across th.ec mitochondrial. membrane whielh regulates glucon eogenesis by outwar(d transport, and citric acid cycle activity by inward transport.
JOHN R. WILLIAMSON 1I. SCHOL2Z
University of Pennsylvania
Blinks, Lawrence R ................................................ 223 Breit, G ........................................................ 223 Chance, B., C. P. Lee, L. Mela, A. Azzi, and C. K. Radda .............. 224 Cole, Kenneth S., Choh-Luh Li, and Anthony F. Bak ................... 225 Davis, Bernard D., and Juan M\odolell ............................... 226 Dean, Christopher S., and D. Stanley Tarbell ......................... 226 Duffin, R. J., and C. Zener ..................... 226 Fraenkel, G., and Jan Zdarek ...................................... 227 Horecker, B. L., R. Gracy, A. Lacko, L. Davis, and R. Adelman ........ 227 Kenney, Francis T., Kai-Lin Lee, and Jerry R. Reel ................... 228 Onsager, Lars, and Mou-Shan Chen ................................. 229 Polis, B. David, Anna Marie Pakoskey, and H. W. Shmukler ........... 229 Shockley, W ...................................................... 230 Sperry, Roger W .................................................. 230 Williams, Carroll M., and Michael P. Kambysellis .................... 231 Williamson, John R., and R. Scholz ................................. 231
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