Deductive biology—Some cautious steps

For certain environments, the Darwinian model allows unique prediction of a function that any surviving system adapted to such an environment has to perform. This is the case for those environments that determine a “survival functional” of position in space-time of known shape. Purely temporal survival functionals can be distinguished from spatial and mixed ones. In each case, there exists an optimum path in combined physical and (reduced) metabolic space. Dependent on the admissible error, approximate solutions of different complexity are sufficient. All solutions possess an afferent, a central, and an efferent part. Within this general frame, specific, “probably simplest”, solutions are proposed for adaptive chemotaxis, insect locomotion, lower vertebrates locomotion, higher vertebrates locomotion, chronobiological systems, and immune systems, respectively—or rather, for the underlying functionals. Presented at the Society for Mathematical Biology Meeting, University of Pennsylvania, Philadelphia, August 19–21, 1976.     

Repeated characterization, analysis of variance limitation and discrimination analysis classification of EEG-activity patterns in human sleep]

1. To describe quantitatively and to deliminate nine EEG sleep patterns, mean values and standard deviations of abundances of the frequencies 0.8 ... 1.8 c/sec, 2...3.5 c/sec, 4...13c/sec, 14 to 17 c/sec, 18 to 22 c/sec, and 23 to 40 c/sec as well as of the average amplitudes in selected frequency ranges were calaculated and the distributions represented. 2. All nine EEG activity patterns could be separated by means of univariate and multivariate analyses of variance on the basis of all 28 as well as the 17 indispensable variables. 3. In the course of a stepwise reduction of variables within the framework of a linear discriminant analysis an optimal set of 17 variables was determined for the separation of the patterns, comprising: the percent quantity of the frequencies 0.8 ... 3.5 c/sec, 7 ... 9 c/sec and 18 to 40 c/sec as well as the average amplitudes in the frequency ranges 0.8 to 3.5 c/sec and 7.5 to 40 c/sec. 4. By linear regression analyses it could be shown that the sleep scording system used, can be reflected on an interval scale with the aid of discriminant functions; this can be achieved on the basis of the optimal set of variables as well as of the five most indispensable variables. 5. Finally the degree of the objectivity of the scoring procedures was demonstrated. Advantages and disadvantages of sleep scoring systems were discussed and possibilities of the utilization of results suggested, also in respect to the further development of the automatic recognition of EEG activity patterns.     

Strukturanalyse der methyl-2,3,6-tridesoxy-2-C-[2-hydroxy-1,1-(Äthylendithio)Äthyl]-α-l-threo-hexopyranosid-4-ulo-22,4-pyranose

Methyl 2,3,6-trideoxy-2-C-[2-hydroxy-1,1-(ethylenedithio)ethyl]-α-l-threo-hexopyranosid-4-ulo-2²,4-pyranose (1) crystallizes in a rhombic space group P2₁2₁2₁ with four molecules in the elementary unit. The structure was refined to an R-value of 0.057. The aldopyranose ring adopts a ¹C₄ conformation with an axial side-chain forming a hemiacetal ring to the keto group at C-4. Both six-membered rings connected in the 2,7-dioxabicyclo[3.3.1]nonane system differ only slightly from the ¹C₄ chair conformation. The spirocyclic dithiolane ring adopts a nearly ideal envelope form with a deviation of C-21 from the plane S-1-C-7-S-2-C-22. The dihedral angle O-5-C-1 O-1-C-11 of 59.1° is an agreement with the exo-anomeric effect.     

Wild Animal Mycobacterial Isolates

Thirteen strains of mycobacteria isolated from deer and various species of wild birds were analysed by gas chromatography (GG) for cellular fatty acids and by thin-layer chromatography (TLG) for polar lipids. These strains were compared to reference strains of Mycobacterium avium, M. para tuberculosis and M. mal-moense. All the examined strains exhibited a generally similar fatty acid pattern characterized by relatively large amounts of hexadenca-noate (16:0), octadecenoate (18:1), octadecanoate (18:0) and 10-me-thyl-octadecanoate (tuberculostearic acid, 10-Me-18:0). Several additional acids were also generally present but in smaller amounts. By means of small but distinct differences in fatty acid composition, the wild animal isolates could be distinguished from both M. paratuber-culosis and M. malmoense but not from M. avium. The TLG polar lipid patterns on the other hand separated the wild animal isolates into 2 distinct groups of complex and simple polar lipid composition which corresponded to the morphologically smooth and rough types, respectively. The complex patterns of the smooth strains were comparable to those of the M. avium serovars whereas both the rough wild animal isolates and all the M. paratuber-culosis strains showed a simple pattern of polar lipids. Both fatty acid profiles and TLG polar lipid patterns support allocation of the wild animal isolates to the MAIS complex. Moreover, the 2 chemical techniques, particularly the GC procedure, are very useful for a more rapid and precise identification of the slow-growing wild animal mycobacterial isolates which have hitherto been characterized on basis of vague criteria.     

Esr,a second locus in the house mouse controlling esterase-5

Electrophoretic variation characterized by the presence (ES-5B⁺) or absence (ES-5B^–) of esterase-5B in the plasma of the house mouse has been observed. It is suggested that the expression of esterase-5B is controlled by an autosomal locus, Esr, linked to Ldr-1 on chromosome 6, in addition to the presumptive structural locus Es-5, which is located on chromosome 8. A gene order of Lyt-3-Esr-Ldr-1 was determined by two crosses.Supported by the Deutsche Forschungsgemeinschaft (SFB 46).This is communication No. 33 of a research program devoted to the investigation of cellular distribution and genetics of nonspecific esterases.     

Bacteriorhodopsin mutants containing single substitutions of serine or threonine residues are all active in proton translocation.

To study their role in proton translocation by bacteriorhodopsin, 22 serine and threonine residues presumed to be located within and near the border of the transmembrane segments have been individually replaced by alanine or valine, respectively. Thr-89 was substituted by alanine, valine, and aspartic acid, and Ser-141 by alanine and cysteine. Most of the mutants showed essentially wild-type phenotype with regard to chromophore regeneration and absorption spectrum. However, replacement of Thr-89 by Val and of Ser-141 by Cys caused striking blue shifts of the chromophore by 100 and 80 nm, respectively. All substitutions of Thr-89 regenerated the chromophore at least 10-fold faster with 13-cis retinal than with all-trans retinal. The substitutions at positions 89, 90, and 141 also showed abnormal dark-light adaptation, suggesting interactions between these residues and the retinylidene chromophore. Proton pumping measurements revealed 60-75% activity for mutants of Thr-46, -89, -90, -205, and Ser-226, and about 20% for Ser-141----Cys, whereas the remaining mutants showed normal pumping. Kinetic studies of the photocycle and of proton release and uptake for mutants in which proton pumping was reduced revealed generally little alterations. The reduced activity in several of these mutants is most likely due to a lower percentage of all-trans retinal in the light-adapted state. In the mutants Thr-46----Val and Ser-226----Ala the decay of the photointer-mediate M was significantly accelerated, indicating an interaction between these residues and Asp-96 which reprotonates the Schiff base. Our results show that no single serine or threonine residue is obligatory for proton pumping.     

A new 440-kD isoform is the major ankyrin in neonatal rat brain

This report describes initial characterization of a 440-kD isoform of brain ankyrin (ankyrinB) representing an alternatively spliced mRNA product of the gene encoding the major isoform of ankyrin in adult human brain (Otto, E., M. Kunimoto, T. McLaughlin, V. Bennett, J. Cell Biology. 114:241-253). Northern and immunoblot analyses indicate that 440-kD ankyrinB includes the spectrin and membrane-binding domains as well as a regulatory domain of the major 220-kD isoform. 440-kD ankyrinB contains, in addition, a sequence of a predicted size of 220 kD which is inserted between the regulatory domain and spectrin/membrane-binding domains. 440-kD ankyrinB has properties expected of a peripherally associated membrane-skeletal protein: it is exclusively present in the particulate fraction of brain homogenates, is extracted with NaOH, and remains associated with Triton-X-100-resistant structures. Expression of 440-kD ankyrinB in rat brain began at birth before other ankyrins could be detected, peaked 10 d after birth, and then decreased progressively to 30% of the maximum in adults. Expression of the 220-kD ankyrinB and ankyrinR (erythroid ankyrin) began approximately 10 d after the 440-kD isoform, increased rapidly between 10 and 15 d after birth, and finally achieved their maximal levels in adults. 440-kD ankyrinB is present in approximately equivalent amounts in all regions of neonatal brain while in adult brain it is present in highest levels in cerebellum and lowest in brain stem. 440-kD ankyrinB was localized by immunofluorescence in regions of neonatal and adult brain containing primarily dendrites and unmyelinated axons. 440-kD ankyrinB thus may play a specialized role in neuronal processes.     

Lewontin and Kojima Meet Fisher: Linkage in a Symmetric Model of Sex Determination

The effect of linkage and epistasis on the evolution of the sex-ratio is studied in a symmetric two-locus model of autosomal sex determination closely related to the symmetric viability model of R. C. Lewontin and K. Kojima. R. A. Fisher's expectation of an even sex ratio for autosomal sex determination by a single gene governs the dynamics when the loci are tightly linked. However, recombination may preclude optimization of the sex ratio just as occurs in viability selection models. Many of the evolutionary phenomena known for the symmetric viability model also occur here. In addition, we exhibit a series of new phenomena related to the presence of surfaces of even sex ratio.     

In vivo binding and clearance of circulating antigen by bispecific heteropolymer-mediated binding to primate erythrocyte complement receptor.

We have used the avidin/biotin system to construct soluble, cross-linked bispecific heteropolymers containing mAb to both the primate E C receptor and the DNP group. These heteropolymers facilitate in vitro binding of DNP-bovine gamma-globulin (DNP-BGG) to both human and squirrel monkey E. Intravenous injection in squirrel monkeys of DNP-BGG followed by heteropolymer leads to E binding and clearance from the circulation of a significant fraction of both heteropolymer and DNP-BGG, without lysis or clearance of the E. This methodology may potentially be used to treat a variety of infectious diseases and other syndromes associated with blood-borne pathogens.     

Genetic and biochemical characterization of a new chymotrypsin isozyme of the house mouse,CTRA-1

Genetic variation of a codominantly inherited pancreas protease, designated CTRA-1, was discovered in the house mouse by isoelectric focusing in polyacrylamide gels. Phenotype CTRA-1A was found in MOLH/Fre and in the majority of common laboratory mouse strains. Phenotype CTRA-1B was found in PWD/Ph. It was characterized by the absence of a corresponding protease band. A third phenotype, CTRA-1C, was observed in IS/Cam and a fourth phenotype, CTRA-1D, was detected in SEG/1. CTRA-1 was found only in the pancreas and may represent the A form of chymotrypsin. The enzyme was shown to be controlled by the presumed structural locus Ctra-1 located on chromosome 8. From two backcross series, including a total of 274 animals, the gene order (Es-1, Es-9)-3.9 +/- 1.7%-Got-2-3.9 +/- 1.7%-(Es-2, Es-7, Es-23)-0.7 +/- 0.5%- Ctra-1-6.3 +/- 2.2%-Prt-2 was established.