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Integrating databases and expert systems for the analysis of brain structures: connections, similarities, and homologies.

The NeuroHomology Database system (NHDB) combines databases related to brain structures from different species with different knowledge management systems (KMSs) for systematization, evaluation and processing neurobiological data. Special attention is assessment of similarity of data from different species as a basis for exploring neural homologies. NHDB includes modules that handle brain structure and connectivity data, as well as inference engines for evaluation of the stored neurobiological information. The spatial inference engine evaluates the possible topological relations between cortical structures in different neuroanatomical atlases. The connectivity inference engine evaluates the reliability of information pertaining to fiber tracts as those are reflected in the literature. The inference engine for translation of neuroanatomical connections in different atlases evaluates the probability of existence of connections of interest in different parcellation schemes. Finally, the similarity inference engine calculates the overall degree of similarity of pairs of brain structures from different species by taking into account a set of eight criteria. We present examples of search for information in NHDB system, inferences of relations between cortical structures from equivalent neuroanatomical atlases, reconstruction of functional networks of brain structures from data collated from the literature, translation of connectivity matrices in equivalent parcellation schemes, and evaluations of similarities of brain structures from humans, macaques and rats.

Algorithms↗

Specific binding of phorbol ester tumor promoters to mouse tissues and cultured cells.

Phorbol esters bind to mouse tissues and chick embryo fibroblasts in a specific, saturable, and reversible fashion. The binding site, located in the membrane fraction, is heat and protease sensitive. Binding can be measured most readily with [3H]PDBu. Binding of [3H]PDBu is of high affinity and is inhibited competitively by nonradioactive phorbol esters; the dissociation constants of the phorbol esters correspond quantitatively to their respective biological and tumor-promoting activities. Of particular significance, highly inflammatory but weakly promoting or nonpromoting diterpene esters are much less potent than PMA. Binding of [3H]PMA has been measured directly. The results confirm that PMA and PDBu interact at the same major high-affinity binding site. [3H]PDBu binding is entropy driven. The equilibrium dissociation constant is independent of temperature, whereas the off-rate is highly temperature dependent. In vivo, specific binding activity increases during embryonic development. It also shows considerable variation among tissues. In the mouse, highest binding activity, 28 pmole/mg, is in the brain (skin, for example, binds 3.9 pmole/mg). Between regions of he brain, 10-fold differences in binding activity are found. The high level of phorbol ester binding in brain suggests that the phorbol ester receptor plays a functional rather than an exclusively information-transducing role in the cell. Growth of cells in the presence of PDBu causes marked down-modulation of phorbol ester receptors. In the GH4C1 rat pituitary cell line, receptor number is decreased by 80% in 24 hr. In membrane preparations, the phorbol ester binding affinity is calcium sensitive. It has been speculated that endogenous ligands interacting at the phorbol ester receptor may exist. The finding that the supernatant fraction from boiled or acidified brain inhibits [3H]PDBu binding is therefore exciting.

Animals↗

Emx and Otx homeobox genes in the developing mouse brain.

We have analyzed the expression of four mouse homeobox genes related to two Drosophila genes expressed in the developing head of the fly. Two of these genes, Emx1 and Emx2, are related to empty spiracles, and two genes, termed Otx1 and Otx2, are related to orthodenticle. These genes are all expressed in the developing rostral brain of E10 mouse embryos and their expression domains can be compared. Otx2 is expressed in all dorsal and most ventral regions of telencephalon, diencephalon, and mesencephalon. The Otx1 expression domain is similar to that of Otx2, but smaller and contained within it. The Emx2 expression domain is comprised of dorsal telencephalon and small diencephalic regions, both dorsally and ventrally. Finally, Emx1 expression is exclusively confined to the dorsal telencephalon. At the time when regional specification of major brain regions takes place, the expression domains of the four genes appear to be continuous regions contained within each other in the sequence Emx1 < Emx2 < Otx1 < Otx2. The first appearance of transcripts of the four genes is also sequential: Otx2 is expressed first (E5.5), followed by Otx1 and Emx2 (E8-8.5), and finally by Emx1 (E9.5). It is tempting to speculate about a possible role of the four genes in establishing and/or signalling the limits of the various embryonic brain regions in a discrete progressive process with its center in the dorsal telencephalon.

Animals↗

Human altruism: economic, neural, and evolutionary perspectives.

Human cooperation represents a spectacular outlier in the animal world. Unlike other creatures, humans frequently cooperate with genetically unrelated strangers, often in large groups, with people they will never meet again, and when reputation gains are small or absent. Experimental evidence and evolutionary models suggest that strong reciprocity, the behavioral propensity for altruistic punishment and altruistic rewarding, is of key importance for human cooperation. Here, we review both evidence documenting altruistic punishment and altruistic cooperation and recent brain imaging studies that combine the powerful tools of behavioral game theory with neuroimaging techniques. These studies show that mutual cooperation and the punishment of defectors activate reward related neural circuits, suggesting that evolution has endowed humans with proximate mechanisms that render altruistic behavior psychologically rewarding.

Altruism↗

Brain size matters: a reply to Peters.

Peters (1993) claimed that published research on brain size and IQ is flawed because it did not meet his list of "minimum conditions" that (a) subjects should be matched for height, weight and age, (b) analyses should be conducted separately within sex, (c) subjects should not vary in prenatal and nutritional history, (d) people with IQS appreciably below the population mean of 100 should not be studied, and (e) brain size measures should be done "blind". However, these "conditions" have either been met or are unnecessary and/or inappropriate. We show, contrary to Peters' claims, that (a) brain size is related to mental abilities, (b) brain size varies by sex and race, and (c) mental abilities vary by sex and race. Finally, we suggest that brain size constraints on behavioural complexity may be best understood from an evolutionary perspective.

Behavior↗

The emergence of humans: the coevolution of intelligence and longevity with intergenerational transfers.

Two striking differences between humans and our closest living relatives, chimpanzees and gorillas, are the size of our brains (larger by a factor of three or four) and our life span (longer by a factor of about two). Our thesis is that these two distinctive features of humans are products of coevolutionary selection. The large human brain is an investment with initial costs and later rewards, which coevolved with increased energy allocations to survival. Not only does this theory help explain life history variation among primates and its extreme evolution in humans; it also provides new insight into the evolution of longevity in other biological systems. We introduce and apply a general formal demographic model for constrained growth and evolutionary tradeoffs in the presence of life-cycle transfers between age groups in a population.

Animals↗

[Brain cholesterol in representatives of different vertebrate classes].

Studies have been made on the cholesterol content of the brain in 73 species of vertebrates. Cholesterol content increases in both aquatic and terrestrial animals in evolutionary row. Significant variations in cholesterol content were noted within the same class. Comparative studies revealed correlation between changes in phospholipids and cholesterol on one hand and various glycolipids on the other. It is suggested that cholesterol content of the brain in vertebrates depends on ecological factors rather than on taxonomic position of animals.

Animals↗

[A general biological hypothesis on the mechanisms of the effect of different psychotropic agents that optimize memory].

Possibility of interpretation of the effects of psychotropic drugs on memory is considered from the viewpoint of general biological conception on molecular mechanisms of memory. Previous studies of functional-molecular mechanisms of memory in animals at different evolutionary levels, carried out by the author and collaborates, became a theoretical basis of the hypothesis proposed. In particular, genome modification was established to be induced by learning and specific and universal components of memory were revealed. Possibility of genome activation in the brain is considered as one of deciding factors in the mechanism of memory optimization by psychotropic drugs.

Animals↗

Evolution of sexual dimorphism in the olfactory brain of Hawaiian Drosophila.

In the fruitfly, Drosophila melanogaster, mate choice during courtship depends on detecting olfactory cues, sex pheromones, which are initially processed in the antennal lobe (AL), a primary olfactory centre of the brain. However, no sexual differences in the structure of the AL have been found in Drosophila. We compared the central brain anatomy of 37 species of Drosophilidae from the islands of the Hawaiian archipelago, uncovering an extreme sexual dimorphism within the AL in which two out of the 51 identifiable glomeruli were markedly enlarged in males. A phylogeny indicated that the sexual dimorphism of the homologous glomeruli arose 0.4-1.9 Myr ago independently in two species groups of Hawaiian endemic Drosophilidae. The corresponding glomeruli in D. melanogaster were also found to be sexually dimorphic. The formation of glomeruli of male size is prevented by the ectopic expression of female-type transformer (tra) cDNA in males, indicating that the glomerular sexual dimorphism is under the control of the sex-determination cascade of genes. It is suggested that a defined set of glomeruli in Drosophila can enlarge in response to sex-determination genetic signals, the mutations of which may result in species differences in sexual dimorphism of the brain.

Animals↗

Distinct sequence of gonadotropin-releasing hormone (GnRH) in dogfish brain provides insight into GnRH evolution.

In vertebrates, gonadotropin-releasing hormone (GnRH) belongs to a family of decapeptides characterized by the conservation of residues 1, 2, 4, 9, and 10. In the jawed vertebrates only positions 5, 7, and 8 in the GnRH molecules vary. We have now purified two forms of GnRH from the brains of spiny dogfish (Squalus acanthias) by using reverse-phase high-performance liquid chromatography. The primary structures were established by automated Edman degradation and mass spectral analysis. The distinct structure of the first form (dogfish GnRH) is pGlu-His-Trp-Ser-His-Gly-Trp-Leu-Pro-Gly-NH2 (pGlu represents pyroglutamyl). The second peptide is identical to a form of GnRH originally isolated from chicken brains (chicken GnRH-II; pGlu-His-Trp-Ser-His-Gly-Trp-Tyr- Pro-Gly-NH2) and is widespread throughout the vertebrates. We are aware of no other species of cartilaginous fish in which the primary structures of two forms of GnRH have been determined. The presence of chicken GnRH-II in dogfish supports the idea that chicken GnRH-II is the oldest GnRH to evolve in jawed vertebrates. With the addition of the dogfish GnRH structure to the family, two main structural branches of GnRH can be delineated. The physiological effects of dogfish GnRH included the release of not only gonadotropin but also growth hormone from goldfish pituitary fragments.

Amino Acid Sequence↗

Evolutionary expression of the neuronal form of the src protein in the brain.

The protooncogene src encodes two proteins, designated pp60c-src+ and pp60c-src.pp60c-src+ is expressed only in neurons, whereas pp60c-src is expressed in neuronal and nonneuronal cells. pp60c-src+ differs from pp60c-src in that it contains an insert of 6 amino acids. To study the evolutionary conservation of the 6-amino acid insert, the expression of pp60c-src+ in the brain of animals from different classes was assayed by using pp60c-src+-specific antibodies raised against a synthetic peptide corresponding to the insert. pp60c-src+ was detected only in the brain of mammals, birds, and reptiles, but not amphibians and fish, whereas pp60c-src was present in the brain of all animals tested, including lobster (invertebrate). These findings indicate that pp60c-src+ may play a role in events associated with higher brain function, such as neuronal plasticity.

Amino Acid Sequence↗

A comparative analysis of brain size in relation to foraging ecology and phylogeny in the Chiroptera.

Variations in total brain mass and in the mass of three brain regions (main olfactory bulb, hippocampus, auditory nuclei) were examined using a data set for 63 species of bats (Chiroptera). Using both conventional and phylogenetically based analysis of covariance (log body mass as covariate), we tested several hypotheses that relate total brain mass or the size of the components to variation in foraging ecology, categorized as phytophagous, gleaner, and aerial insectivore. In some analyses, the category phytophagous was split into phytophagous pteropodid and phytophagous phyllostomid to examine differences between two distinct clades of bats. Because the Megachiroptera orient primarily by vision and olfaction, whereas all other bats rely on laryngeal echolocation to locate their prey, we hypothesized that the former would differ in size of the main olfactory bulb, as compared with all other bats. This hypothesis was supported by our analyses. Our more general prediction was that insectivorous bats, which rely heavily on echolocation for the pursuit and capture of their prey, would have larger auditory nuclei than do phytophagous species. This, too, was supported. We also compared phytophagous (fruit or nectar consuming) bats in two families, the Pteropodidae and the Phyllostomidae. We hypothesized that the phyllostomids, which use echolocation while foraging, would have larger auditory nuclei. Although statistical power is low in phylogenetically informed comparisons of the two clades, we did find weak evidence in support of this hypothesis. We conclude that bat brains show evidence of adaptation to foraging ecology.

Adaptation, Physiological↗

Further exploration into the adaptive design of the arthropod "microbrain": I. Sensory and memory-processing systems.

Arthropods have small but sophisticated brains that have enabled them to adapt their behavior to a diverse range of environments. In this review, we first discuss some of general characteristics of the arthropod "microbrain" in comparison with the mammalian "megalobrain". Then we discuss about recent progress in the study of sensory and memory-processing systems of the arthropod "microbrain". Results of recent studies have shown that (1) insects have excellent capability for elemental and context-dependent forms of olfactory learning, (2) mushroom bodies, higher olfactory and associative centers of arthropods, have much more elaborated internal structures than previously thought, (3) many genes involved in the formation of basic brain structures are common among arthropods and vertebrates, suggesting that common ancestors of arthropods and vertebrates already had organized head ganglia, and (4) the basic organization of sensori-motor pathways of the insect brain has features common to that of the mammalian brain. These findings provide a starting point for the study of brain mechanisms of elaborated behaviors of arthropods, many of which remain unexplored.

Animals↗

NADPH:cytochrome P-450(c) reductase: biochemical characterization in rat brain and cultured neurons and evolution of activity during development.

NADPH:cytochrome P-450 (c) reductase is a microsomal enzyme which is involved in the cytochrome P-450-dependent biotransformation of many exogenous agents as well as of some endogenous molecules. Using cytochrome c as a substrate, the kinetic parameters of this enzyme were determined in brain microsomes. The comparison of the NADPH:cytochrome P-450 reductase's Vmax values and cytochrome P-450 contents in both fractions, suggests a role of cerebral NADPH:cytochrome P-450 reductase in cytochrome P-450 independent pathways. This is also supported by the different developmental pattern of brain enzyme as compared to the liver enzyme, and by the presence of a relatively high NADPH:cytochrome P-450 reductase activity in immature rat brain and neuronal cultures, while cytochrome P-450 was hardly detectable in these preparations. The enzyme activity was not induced by a phenobarbital chronic treatment neither in the adult brain nor in cultured neurons, suggesting a different regulation of the brain enzyme expression.

Animals↗

Evolutionary comparison of enzyme activities of phosphatidylcholine metabolism in the nervous system of an invertebrate (Loligo pealei), lower vertebrate (Mustelus canis) and the rat.

While steady-state kinetic parameters (metabolite pools, Km and activation energies) are partially known for the enzymes involved in phosphatidylcholine synthesis and degradation in mammalian brain, they are not available for the nervous system of lower vertebrates or invertebrates. Since the extent of evolutionary development of an enzyme is not known a priori, we evaluated the kinetic and thermodynamic parameters of choline kinase, CTP:phosphocholine cytidylyltransferase, choline phosphotransferase and glycerophosphorylcholine phosphodiesterase in squid (Loligo pealei) optic lobe, dogfish (Mustelus canis) and rat brain. For all these enzyme activities, basic similarities in Km and inhibitor effect were found. The same was true for the activation energies Ea, with the exception of squid choline kinase and dogfish cytidylyltransferase. Treatment of microsomal membranes with phospholipase C sharply inhibited cytidylyltransferase activity in all three animal species. In dogfish brain, glycerophosphorylcholine phosphodiesterase activity was undetectable. Our results are consistent with the notion that the kinetic properties of the enzyme activities leading to the preservation of the phosphatidylcholine membranous pool may have appeared early in metazoan evolution and been fully conserved in mammals.

Animals↗