Cell surface glycosyltransferase activities during normal and mutant (TT) mesenchyme migration

Migrating cells possess surface glycosyltransferase activity toward extracellular substrates, and the appearance of enzyme activity coincides with the onset of cellular migration (Shur, 1977a, Shur, 1977b, Develop. Biol.58, 23–39, 40–55; E. A. Turley and S. Roth, 1979, Cell17, 109–115). In this paper, surface glycosyltransferases were examined during normal and $\text{T}\text{T}$ mutant mesenchyme migration. Of six glycosyltransferases that were assayed, only galactosyltransferase was present at significant levels on the cell surface, despite the presence of a variety of intracellular glycosyltransferases. All controls have been performed to show clearly the enzyme activity was cell surface localized. In both normal and $\text{T}\text{T}$ embryos, surface galactosyltransferase activity was localized, by autoradiography, primarily to migrating mesenchymal cells, and to a lesser degree, to presumptive neural epithelium. During primitive streak formation, putative $\text{T}\text{T}$ embryos were devoid of surface galactosyltransferase activity. However, as development progressed, the $\text{T}\text{T}$ level of activity eventually exceeded wild-type levels by two- to sixfold and was evident in $\text{T}\text{T}$ tissues prior to the onset of microscopic pathology. Other surface enzymes assayed did not show any $\text{T}\text{T}\text{-}\text{dependent}$ increase in activity. The extracellular galactosyl acceptors were not chloroform:methanol soluble, and glycopeptides prepared by exhaustive Pronase digestion were excluded from Sephadex G-50. This large galactosylated glycoconjugate was readily digestable with endo-β-galactosidase, and, therefore, is similar to the poly-N-acetyllactosamine chains previously identified on early embryonic tissues (A. Kapadia, T. Feizi, and M. J. Evans, 1981, Exp. Cell. Res.131, 185–195; T. Muramatsu, G. Gachelin, M. Damonneville, C. Delarbre, and F. Jacob, 1979, Cell18, 183–191; A. Heifetz, W. J. Lennarz, B. Libbus, and Y. -C. Hsu, 1980, Develop. Biol.80, 398–408). These results support an involvement of surface galactosyltransferases in mesenchyme formation and during migration on poly-N-acetyllactosamine substrates.     

Unified theory of 1f and conductance noise in nerve membrane

A theory of $\text{1}\text{f}$ and conductance noise is given for ionic channels in nerve membrane. The theory is based on the assumption that the channels are in constant, stochastically independent, rotational motion within a fluid bilayer membrane. The resulting expression for the current noise power density S contains a conduction noise term consistent withStevens (1972) and Hill & Chen (1972) and a $\text{1}\text{f}$ noise term consistent with Lundstrom & McQueen (1974) and Clay & Shlesinger (1976). The expression for S also contains a third term which is the spectrum of the product of the single channel conduction noise and $\text{1}\text{f}$ noise correlation functions. This term is independent of the number of channels in the membrane, R. Consequently, the expression for S effectively reduces to a sum of $\text{1}\text{f}$ and conduction noise for R 10–100 which is in agreement with noise measurements on squid axon. The theory is applied in detail to potassium squid noise measurements of Conti, DeFelice & Wanke (1975) using the stochastic analysis of single file ion motion developed in our previous paper (Clay & Shlesinger (1976)).     

Regulation of coenzyme utilization by the dual nucleotide-specific glucose 6-phosphate dehydrogenase from Leuconostoc mesenteroids.

The dual wavelength assay technique (H. R. Levy, and G. H. Daouk, 1979, J. Biol. Chem.254, 4843–4847) is used to examine the rates of the NADP- and NAD-linked reactions of Leuconostoc mesenteroides glucose 6-phosphate dehydrogenase simultaneously under various conditions. Inhibition by ATP, MgATP^2?, acetyl-CoA, and palmitoyl-CoA is greatly diminished at high glucose 6-P concentration which favors the NAD-linked reaction. Increasing $\text{NADPH}\text{NADP}{}^{\mathrm{+}}$ concentration ratios inhibit the NADP-linked, but stimulate the NAD-linked reaction. The selective effects of glucose 6-P and the $\text{NADPH}\text{NADP}{}^{\mathrm{+}}$ concentration ratio, which cannot be detected by conventional assays, are explained in terms of the differing kinetic mechanisms for the NADP-linked and NAD-linked reactions previously described (C. Olive, M. E. Geroch, and H. R. Levy, 1971, J. Biol. Chem.246, 2047–2057). It is proposed that these effects constitute the mechanism whereby the nucleotide specificity of the amphibolic glucose 6-phosphate dehydrogenase from Leuconostoc mesenteroides is regulated.     

The role of migration in the genetic structure of populations in temporally and spatially varying environments II. Island Models

The Island Model introduced by Sewall Wright (1951) has proven to be a useful construction for studying the interaction of genetic drift, population subdivision, and mutation. Interest in the model has recently increased because of its relevance to certain questions involving the rate of differentiation of sub-populations under the neutral allele hypothesis (e.g., Smith, 1970; Latter, 1973). It is perhaps the only realistic population structure in which the test for neutrality proposed by Lewontin and Krakauer (1973) is valid (Lewontin and Krakauer, 1975). If data from natural populations is to be compared to the predictions of the Island Model, it is desirable to have an alternative model with the same migration pattern but with natural selection operating. In this paper one such model will be introduced where the stochastic element comes from random fluctuations in the environment rather than from genetic drift. The model is a direct extension of the one in the previous paper in this series (Gillespie, 1975) which dealt with a population which is subdivided into two patches with restricted migration between them.     

An autoradiographic analysis of the time of appearance of neurons in the developing chick neural retina

The pattern of incorporation of [³H]thymidine into the chick neural retina has been used to establish the time and order in which different classes of neuroepithelial cells withdraw from the cell cycle and initiate migration and differentiation.The posterior pole of the retina is the first to form during development. In this region most neuroepithelial cells complete mitotic activity between the third and sixth day of incubation. Presumptive ganglion cells initiate the withdrawal process, and they are soon followed by the neuroepithelial precursors of amacrine, horizontal, and receptor cells. Bipolar cell precursors are the last to begin and the last to complete cell cycle activity. It is worthy of note, however, that, in any given region of the retina, neuroepithelial cells of all types cease mitosis in close, overlapping succession.These results are in reasonable agreement with those previously published on the chick retina by Fujita and Horii (1963), and other investigators on the mouse (Mus), killifish (Fundulus), and toad (Xenopus). The present data are also consistent with those proposals of Angevine (1970), Jacobson, 1968a, Jacobson, 1968b, Jacobson, 1970, and others that relate the cessation of mitotic activity of neuroepithelial cells to the determination of neuronal size, axon length, and the specification of neuronal connections.     

Box-Jenkins forecasting in ecology: An answer to poole

This answering of Poole, 1978, Poole, 1976 aims at rounding off our exchange of views, without losing the readership from an excess of toing and froing between the four contributions. So my final rejoinder only attempts at treating the general points raised by Poole (1978), rather than taking issue with all the minutiae, which would require too many quotes of quotes and counterquotes. The main nub of contention remains as to whether or not statistical fits can be meaningfully interpreted biologically.     

Does a functional relationship exist between the polymerization and catalytic activity of beef liver glutamate dehydrogenase?

The recent work of Cohen &; Benedek (1976) and Cohen et al. (1975, 1976) on the apparent interdependence of beef liver glutamate dohydrogenase catalytic activity and degree of polymerization is examined in the light of previously published equilibrium and kinetic results. It is shown that some of the hypotheses central to the Cohen &; Benedek (1976) model are in contradiction with existent data. Consideration of all available information leads to the conclusion that effector-induced depolymerization may simply be an incidental side reaction in the events leading to inhibition.     

Complexity-stability relationship of two-prey-one-predator species system model: Local and global stability

Parrish & Saila (1970), motivated by the experiments of Paine (1966), constructed a simple mathematical model for a two-prey-one-predator system. They were unable to find, in their model, a set of parametric values with which the three-species system can be stable, whereas a twoprey species system without a predator is unstable. Cramer & May (1972) showed that, in fact, such parametric values exist, and gave the necessary mathematical condition. I have investigated the complete conditions for the stability of the system around the equilibrium point, and show that the conditions must be more stringent than given by Cramer & May (1972). Also, it is shown that the present model can have a globally stable limit cycle in three species even when the equilibrium point is locally unstable.     

Studies of the voltage-dependent polyspermy block using cross-species fertilization of amphibians

Fertilization of frog eggs by frog sperm is inhibited if the egg's membrane potential is positive (N. L. Cross and R. P. Elinson, 1980, Dev. Biol.75, 187–198); however, fertilization of salamander eggs by salamander sperm does not depend on membrane potential (M. Charbonneau, M. Moreau, B. Picheral, J. P. Vilain, and P. Guerrier, 1983, Dev. Biol.98, 304–318). Since salamander sperm can fertilize frog eggs, we have investigated whether this cross-fertilization is voltage dependent. If, during insemination with Notophthalmus sperm, Xenopus eggs were voltage clamped between +7 and +20 mV, fertilization proceeded in $\text{7}\text{10}$ (70%) of the clamped eggs, compared to $\text{38}\text{48}$ (79%) of the neighboring eggs. In control experiments in which voltage-clamped Xenopus eggs were inseminated with Xenopus sperm, fertilization proceeded in only $\text{1}\text{10}$ (10%) of the clamped eggs, compared to $\text{59}\text{60}$ (98%) of the neighbors. Similar results were obtained with cross-fertilization experiments between Notophthalmus sperm and Rana eggs. These experiments indicate that the voltage dependence of fertilization depends on the species of sperm.     

Warfare and hominid brain evolution.

This paper reviews literature on the evolutionary effects of warfare upon the hominid brain. Alexander &; Tinkle (1968) and Bigelow (1969) are found to be the first to propose that warfare was the principle evolutionary pressure that created the novel substance of the human brain, and that it acted at least from the early Pleistocene. These writers are distinguished from Darwin (1871), Keith (1947) and Wilson (1975) who saw warfare influencing the development of the brain only in historical or near-historical times.The warfare hypothesis of Alexander &; Tinkle is found to be an excellent explanation of the evolution of the human brain, but to be unsatisfactory from a biological viewpoint because they do not explain how warfare evolved in the first place, nor do they attempt to account for the apparent absence of warfare as a behavioral adaptation in species other than some eusocial insects.This author underpins the warfare hypothesis, arguing that it evolved as a necessary consequence of the circumstances of early hominids. Proficient tool use gave domination over predators and opened up new food resources, thereby diminishing two population controls. A population explosion resulted and, at critical densities, when starvation threatened, warfare was the genetically most successful behavioral adaptation. Alternative hypotheses are shown to be inadequate. Finally, the author asks why such an important hypothesis has been ignored for almost a decade.     

Visualization of drug--nucleic acid interactions at atomic resolution. V. Structure of two aminoacridine--dinucleoside monophosphate crystalline complexes, proflavine--5-iodocytidylyl (3'-5') guanosine and acridine orange--5-iodocytidylyl (3'-5') guanosine

Acridine orange and proflavine form complexes with the dinucleoside monophosphate, 5-iodocytidylyl(3′–5′)guanosine. The acridine orange-iodoCpG² crystals are monoclinic, space group P2₁, with unit cell dimensions $\text{a = 14.36}\text{A}\text{?}\text{, b = 19.64}\text{A}\text{?}\text{, c = 20.67}\text{A}\text{?}$, β = 102.5 °. The proflavine-iodoCpG crystals are monoclinic, space group C2, with unit cell dimensions $\text{a = 32.14}\text{A}\text{?}\text{, b = 22.23}\text{A}\text{?}\text{, c = 18.42}\text{A}\text{?}$, β = 123.3 °. Both structures have been solved to atomic resolution by Patterson and Fourier methods, and refined by full matrix least-squares.Acridine orange forms an intercalative structure with iodoCpG in much the same manner as ethidium, ellipticine and 3,5,6,8-tetramethyl-N-methyl phenanthrolinium (Jain et al., 1977, Jain et al., 1979), except that the acridine nucleus lies asymmetrically in the intercalation site. This asymmetric intercalation is accompanied by a sliding of base-pairs upon the acridine nucleus and is similar to that observed with the 9-aminoacridine-iodoCpG asymmetric intercalative binding mode described in the previous papers (Sakore et al., 1977, Sakore et al., 1979). Basepairs above and below the drug are separated by about 6.8 Å and are twisted about 10 °; this reflects the mixed sugar puckering pattern observed in the sugar-phospate chains: C3′ endo (3′–5′) C2′ endo (i.e. each cytidine residue has a C3′ endo sugar comformation, while each guanosine residue has a C2′ endo sugar conformation), alterations in glycosidic torsional angles and other small but significant conformational changes in the sugar-phosphate backbone.Proflavine, on the other hand, demonstrates symmetric intercalation with iodoCpG. Hydrogen bonds connect amino groups on proflavine with phosphate oxygen atoms on the dinucleotide. In contrast to the acridine orange structure, base-pairs above and below the intercalative proflavine molecule are twisted about 36 °. The altered magnitude of this angular twist reflects the sugar puckering pattern that is observed: C3′ endo (3′–5′) C3′ endo. Since proflavine is known to unwind DNA in much the same manner as ethidium and acridine orange (Waring, 1970), one cannot use the information from this model system to understand how proflavine binds to DNA (it is possible, for example, that hydrogen bonding observed between proflavine and iodoCpG alters the intercalative geometry in this model system).Instead, we propose a model for proflavine-DNA binding in which proflavine lies asymmetrically in the intercalation site (characterized by the C3′ endo (3′–5′) C2′ endo mixed sugar puckering pattern) and forms only one hydrogen bond to a neighboring phosphate oxygen atom. Our model for proflavine-DNA binding, therefore, is very similar to our acridine orange-DNA binding model. We will describe these models in detail in this paper.     

The Plasmodium vaughani--Complex

Plasmodium vaughaniNovy and MacNeal, 1904, Plasmodium tenueLaveran and Marullaz, 1914, and Plasmodium merulaeCorradetti and Scanga, 1972 are shown to differ. It is suggested that P. tenue and P. merulae should be considered as subspecies belonging to Plasmodium vaughani-complex.More investigations are needed for a sufficient knowledge of the complex, particularly because at least 36 species of birds harbor P. vaughani-like parasites and cover an immense geographical area in all the parts of the world.     

ADP-ribosylation of nuclear protein A24

Nuclear protein A24, which is composed of histone H2A and ubiquitin, a nonhistone protein, joined by an isopeptide linkage [Goldknopf and Busch (1977) $\text{Proc}$. $\text{Natl}$. $\text{Acad}$. $\text{Sci}$. $\text{USA}$$\text{74}$, 864–868], is found to be ADP-ribosylated in isolated rat liver nuclei.     

Identification of the octapeptide [Met]enkephalin -Arg6-Gly7-Leu8 in extracts of bovine adrenal medulla

The primary structure of the 5300 dalton adrenal enkephalin-containing polypeptide was shown to contain at its carboxyl terminus the sequence -Lys-Arg-Tyr-Gly-Gly-Phe-Met-Arg-Gly-Leu-COOH (Jones $\text{et al}$., (1981) Proc. Natl. Acad. Sci. USA, in press). From knowledge of the type of processing that occurs at paired basic amino acid residues such as -Lys-Arg-, it was predicted that the octapeptide Tyr-Gly-Gly-Phe-Met-Arg-Gly-Leu should be produced and exist in free form in the adrenal gland. This octapeptide has now been purified from bovine adrenal chromaffin granules. Its structure was determined by amino acid analysis, carboxypeptidase Y time course hydrolysis and sequential digestion with trypsin and carboxypeptidase B. The octapeptide has 35% the opiate receptor binding activity of [Met]enkephalin.     

Scanning electron microscopy studies of erythrocytes in Huntington's disease.

Scanning electron microscopic study of unmanipulated erythrocytes from Huntington's Disease (HD) patients disclosed an increased number of stomatocytes compared to controls. This morphological alteration may reflect a membrane abnormality and supports our previous electron spin resonance results (Butterfield $\text{et al}$, Nature (1977)$\text{267}$, 453–455) which suggests that HD may have diffuse membrane involvement.