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Anthropological considerations relevant to the maturation of the immune response in humans.

PROBLEM: The reason for the postnatal maturation of the immune response in humans was explored from the anthropological standpoint in order to gain some insight into how development in modern humans evolved and how it might have affected the immune system. METHOD: The estimation of the length of gestation in modern humans if it had followed the same developmental pattern as in the other hominids and the higher primates was calculated by extrapolation from the lengths of gestation and the physical characteristics of these other primates compared to those of modern humans. RESULTS: These calculations show that the gestation time of modern humans would be 3-18 months longer than the 9 months that it is if modern humans had followed a linear evolutionary development comparable to that of the other primates. The key difference between modern humans and the other primates is the rapid and extensive development of the brain that occurs in utero and in the first 12-18 months postnatally in modern humans. CONCLUSION: The first 12-18 months postnatally in humans follows the embryonic/fetal pattern of development, whereas that of other primates does not. The maturation of the immune response in humans occurs during both the intrauterine and extrauterine phases of the embryonic/fetal pattern of development.

Animals↗

The brain of Thylacosmilus atrox. Extinct South American saber-tooth carnivore marsupial.

Two endocasts of the extinct marsupial Thylacosmilus atrox are studied. The specimens were found in outcrops at present considered of Pliocene Age. The followings are the conclusions arrived in the study: 1) The encephalon of Thylacosmilus atrox shows a well developed neocortex, with a deep rhinal fissure and the major marsupial neocortical sulci well observable. The homologies of the sulci was certainly easy in the major part of them, and consequently, functional inferencies were possible. 2) The somatic neocortical area shows certain distinctive characteristics. It appears that the size proportions between the mandibular and maxillary areas is reversed in T. atrox, which appears congruent with the infered function of its peculiar cranial anatomy. 3) The relative brain size of T. atrox is very heigh for a Polyprotodont marsupial being its encephalization quotients and progression indexes at the level of the living Diprotodonta. 4) Thylacosmilus atrox was a very peculiar extinct carnivore marsupial, which at the Late Tertiary in South America reached higher levels of encephalization than the posterior or living representatives of its same Order.

Animals↗

FAC1, a novel gene identified with the monoclonal antibody Alz50, is developmentally regulated in human brain.

The monoclonal antibody Alz50 recognizes both neurofibrillary pathology associated with Alzheimer's disease and subplate neurons in the developing human brain. To attempt to identify Alz50 antigens expressed during development, a human fetal brain cDNA library was immunoscreened. A positive clone was isolated and sequenced. The clone represents a novel gene named FAC1 (Fetal Alz-50-Reactive Clone 1). The FAC1 gene is located on human chromosome 17 and is conserved across species. In the human fetal brain, the FAC1 gene product is abundantly expressed and the protein is located both in the nucleus and the cytoplasm of cells throughout the developing cortex. Decreased levels of FAC1 protein are observed in adult brain by immunoblot analysis. By immunocytochemistry, the FAC1 protein is almost exclusively localized in the nucleus of neurons in the adult neocortex. Therefore, expression of the FAC1 gene is developmentally regulated and the cellular localization of the protein product is altered during development.

Adolescent↗

Two Pax-binding sites are required for early embryonic brain expression of an Engrailed-2 transgene.

The temporally and spatially restricted expression of the mouse Engrailed (En) genes is essential for development of the midbrain and cerebellum. The regulation of En-2 expression was studied using in vitro protein-DNA binding assays and in vivo expression analysis in transgenic mice to gain insight into the genetic events that lead to regionalization of the developing brain. A minimum En-2 1.0 kb enhancer fragment was defined and found to contain multiple positive and negative regulatory elements that function in concert to establish the early embryonic mid-hindbrain expression. Furthermore, the mid-hindbrain regulatory sequences were shown to be structurally and functionally conserved in humans. The mouse paired-box-containing genes Pax-2, Pax-5 and Pax-8 show overlapping expression with the En genes in the developing brain. Significantly, two DNA-binding sites for Pax-2, Pax-5 and Pax-8 proteins were identified in the 1.0 kb En-2 regulatory sequences, and mutation of the binding sites disrupted initiation and maintenance of expression in transgenic mice. These results present strong molecular evidence that the Pax genes are direct upstream regulators of En-2 in the genetic cascade controlling mid-hindbrain development. These mouse studies, taken together with others in Drosophila and zebrafish on the role of Pax genes in controlling expression of En family members, indicate that a Pax-En genetic pathway has been conserved during evolution.

Animals↗

From here to eternity: brain aging in an evolutionary perspective.

There is plenty of evidence to show that a high metabolic rate slowly destabilizes the optimal differentiated state of cells as a result of nonenzymatic processes. Because of the continuing high energy demands of the brain in homeothermic organisms, an evolutionary expansion of this organ has to go with the development of maintenance systems which effectively counteract these degenerative processes. Thus the nerve cells in more encephalized and longer-lived species are probably inherently more stable in maintaining their cellular and molecular integrity in the presence of destabilizing insults than do low encephalized species with short life spans.

Aging↗

The fine structure of lamellate cells in the brain of amphioxus (Branchiostoma lanceolatum, Cephalochordata).

The lamellate cells of amphioxus have round nuclei, and cytoplasm with many mitochondria and a large amount of glycogen. Each of these cells projects a highly modified, branched cilium into the central canal, where it characteristically forms lamellar structures. Primary branches and secondary lamellae often contain accessory microtubules that are not derived from the axonema. The functional and evolutionary significance of this cell type is discussed in relation to the ciliary photoreceptors found in other chordates.

Animals↗

A combined analysis of regional energy metabolism and immunohistochemical ischemic damage in the gerbil brain.

By combining immunohistochemical technique with microassay methods, we analyzed regional energy metabolism in vulnerable and tolerant areas of gerbil brains during evolution of neuronal damage after bilateral common carotid artery occlusion for 10 min with subsequent reperfusion. Four animals were used for each reperfusion period. Based on the information from the immunohistochemical examination, we dissected out vulnerable and tolerant subregions of the hippocampus, cerebral cortex, and thalamus from freeze-dried 20-microm-thick sections, and measured the levels of creatine phosphate (P-Cr), adenine nucleotides, guanine nucleotides, and purine bodies by HPLC, and the levels of glucose, glycogen, and lactate by an enzyme-immobilized column method. There were no significant differences in the levels of metabolites between vulnerable and tolerant subregions of control brains. After reperfusion, both vulnerable and tolerant subregions recovered preischemic metabolic profiles by 2 days. Although the regional differences between vulnerable and tolerant subregions were minimal at each reperfusion period, there were delays in the recovery of P-Cr, ATP, and/or total adenine nucleotides in all vulnerable subregions. A decline of P-Cr, ATP, and GTP levels without change in %ATP, AMP, or purine bodies occurred after reperfusion for 3 days, coinciding with the development of immunohistochemical damage by the immunoreaction for microtubule-associated protein 1A. The results supported the notion that subtle but sustained impairment of energy metabolism caused by mitochondrial dysfunction in the early reperfusion period might trigger delayed neuronal death in vulnerable subregions.

Adenine Nucleotides↗

The forebrain of the Pacific hagfish: a cladistic reconstruction of the ancestral craniate forebrain.

The forebrain of the Pacific hagfish is described with regard to its morphology, cytoarchitecture, and secondary olfactory projections. The forebrain ventricular system is greatly reduced in adult hagfishes, although vestiges of ventricular structures can still be recognized. In order to clarify topographical relationships within the forebrain, we provide a three-dimensional reconstruction of the ventricular system, including the vestigial portions. Topography and embryology lead us to conclude that the 'primordium hippocampi' of previous authors is a diencephalic structure. For topographical and hodological reasons, we interpret the 'area basalis' of previous authors to be part of the preoptic region, and we identify a part of the so-called 'nucleus olfactorius anterior' as the homologue of the striatum. The laminated pallium is dominated by secondary olfactory projections and shows a high degree of regional cytoarchitectural specialization, as does the entire forebrain. In all, 42 cell groups are identified in the forebrain of hagfishes (compared to only about 25 in lampreys, for example). This surprisingly high degree of cytoarchitectural complexity prompted us to re-examine the phylogenetic history of craniate brains with this complexity in mind. In this paper we use cladistic methodology to reconstruct a morphotype, and we conclude that the forebrains of the earliest craniates may have been more complex than previously believed. This reconstruction includes hypotheses regarding the general morphology, secondary olfactory system, and visual system, as well as the relative sizes of major divisions of the forebrain in the earliest craniates.

Animals↗

Encephalization in tropical teleost fishes and comparison with their mode of life.

The brains were dissected from a total of 1225 fishes representing 737 species, 310 genera and 113 families of tropical and subtropical teleosts. Each fish was weighed before brain dissection, and each brain weighed after its removal. The encephalization coefficient k was determined for each fish from a quadratic formula; to conveniently compare brain size of one species with that of another, we used an encephalization index so that an encephalization index of 100 is the average for all the species investigated. The encephalization indices for the families of fishes studied varied from 7 for the Moringuidae to 233 for the Coryphaenidae. There is no strong correlation in relative brain size with phylogenetic position. Although there is a general trend for the more highly evolved fishes to have larger brains, this is partially obscured by some high values in certain primitive groups and low ones in the more advanced. Elongate fishes have lower encephalization indices in general. This may in part be related to low phylogenetic position of most elongate species (anguilliform fishes, for example), in part to the greater relative body weight due to the longer vertebral column (and usually more numerous fin rays as as well), and to their usual mode of swimming by lateral undulations of the body (the most primitive type of aquatic locomotion--one in which the spinal cord plays a major role). No difference could be noted in the encephalization indices of herbivorous families of fishes compared to carnivorous ones. Within a genus, among medium to large-size fishes, those species of larger size tend to have lower encephalization indices. This may be related to larger fishes having less to fear of predators. Fishes which in some passive way avoid predation have low indices in general. This is particularly true of benthic species which conceal themselves by flattened form, fleshy protuberances or protective coloration, or which bury in the sediment or take refuge in burrows. Also correlated with low indices is some form of predator deterence such as production of skin toxins, presence of venomous spines or ability to enlarge the body by inflation. Fishes which have more than a single sense highly developed exhibit a larger relative brain size than those with only one well developed sense. Fishes which live in a complex community of high species diversity, such as a coral reef, have higher indices, in general, than those which dwell on mud and sand flat. Pelagic fishes, such as scombrids and carangids, are among those with the highest indices.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Factors necessary for restoring an evolutionary change in an anural ascidian embryo.

The ascidian Molgula oculata has a tailed (or urodele) larva, whereas Molgula occulta develops directly via a tailless (or anural) embryo. Interspecific hybrid embryos produced by fertilizing M. occulta eggs with M. oculata sperm (M. occulta x M. oculata hybrids) can develop urodele larval structures, including a brain pigment cell and a short tail containing a small notochord. Development of larval features differs in individual M. occulta clutches: some eggs develop into hybrids with both a brain pigment cell and a tail, some into hybrids with either a brain pigment cell or a tail, and others into hybrids without urodele features. The expression of a 58-kDa protein (p58), which is present in eggs and embryos of urodele ascidians but lacking in those of most anural species, also varies in expression between different clutches of M. occulta eggs. Western blot and immunofluorescence studies show that p58 expression is correlated with the ability of hybrid embryos to express urodele features. For example, clutches of M. occulta eggs containing relatively high levels of p58 produce many hybrids with both a brain pigment cell and a tail. Differential expression of p58 occurs during oogenesis in M. occulta individuals: p58 is found at similar levels in previtellogenic oocytes, but in some animals it disappears during vitellogenesis, while in others it persists throughout oogenesis and is present in mature eggs. When M. occulta eggs are extracted with Triton X-100, p58 remains in the detergent-insoluble fraction, suggesting that it is associated with the cytoskeleton. In most unfertilized M. occulta eggs, p58 is uniformly distributed, but after fertilization it is localized in the uncleaved zygote and then concentrated in embryonic ectoderm, notochord, and muscle lineage cells. Despite containing high levels of p58, gynogenetic hybrid embryos, produced by fertilizing M. occulta eggs with uv-irradiated M. oculata sperm, develop into hybrids without a brain pigment cell or a tail. The results suggest that both a functional paternal genome and p58 are necessary for restoration of larval features in M. occulta x M. oculata hybrids. The cytoskeletal complex containing p58 may mediate the localization of key maternal factors in the egg or may be involved in cellular interactions during embryogenesis which are responsible for development of urodele cell fates.

Animals↗

Phylo- and ontogenetic fears and the expectation of danger: differences between spider- and flight-phobic subjects in cognitive and physiological responses to disorder-specific stimuli.

To compare specific phobias with an assumed phylogenetic or ontogenetic origin in responses to fear-relevant (FR) stimuli, 17 spider- and 17 flight-phobic participants were exposed to pictures of spiders, flight accidents, or mushrooms randomly followed by either a startling noise or nothing else. While both groups showed a disorder-specific expectancy bias, only spider-phobic participants exhibited a disorder-specific covariation bias. Spider-phobic participants also showed enhanced skin conductance responses (SCRs), event-related brain potentials (ERPs), and startle responses triggered by disorder-specific FR pictures while flight-phobic participants showed only disorder-specific enhanced SCRs. In sum, our direct comparison between ontogenetic and phylogenetic phobias revealed that the former is characterized by biased and enhanced responses triggered by disorder-specific FR stimuli presumably based on a biological preparedness.

Adult↗

Amino acids and cell regulation.

Free amino play an important role in regulating cell volume in fishes. Four tissues/cells (skeletal muscle, RBC, brain, and myocardium) of the little skate, Raja erinacea, were selected for detailed study because of their special importance or unique advantage as experimental models. Three particular amino acids, beta-alanine, taurine, and sarcosine play a predominant role in all four tissues. As in higher vertebrates, amino acid uptake in skate brain, heart, and RBC is mediated via a Na+-dependent process. Amino acids leave the skate brain rapidly in response to a sudden decrease in plasma osmolality and/or to a simultaneous drop in extracellular Na+ concentration. However, although amino acids are important for volume regulation in normal brain cells, they do not appear to be likely candidates for the unidentified "idiogenic" osmolytes in mammalian brain cells. The high concentration of taurine in skate myocardium is of special interest because of the special role of this amino acid in myocardial contractility. Thus, unlike beta-alanine and sarcosine, taurine may play a dual role in regulating both cell volume and contractility of myocardial cells. The isolated skate atrium is well suited for in vitro studies of these two processes.

Amino Acids↗

Normal computerized tomography of brain in children with shaken baby syndrome.

OBJECTIVE: To characterize the clinical presentation and clinical course of shaken baby syndrome (SBS) with normal cranial computerized tomography (CT) on admission and to suggest further diagnostic procedures in such circumstances. METHODS: Using a worldwide listserv designed to facilitate discussion in the field of child abuse and neglect, we solicited case information for children hospitalized in different medical centers, who were diagnosed with SBS and had a normal CT scan on admission. RESULTS: Nine cases were identified. While all children had an abnormal neurologic examination on admission, eight had a normal CT, and one had "widening of cranial sutures." In four cases, subdural hemorrhage was diagnosed on magnetic resonance imaging (MRI) 3 to 7 days after admission. Five children had bone fractures. The neurological outcome was normal in four of nine cases. Five children had long-term neurologic damage. The diagnosis of SBS was supported by either perpetrator confession, characteristic evolution of brain abnormalities on CT or MRI, inconsistent or absent explanatory history, and/or other social risk factors. CONCLUSION: The diagnosis of SBS can be established even when brain CT is normal on admission. The documentation of retinal hemorrhages is of primary importance in establishing the diagnosis of SBS in these cases.

Brain↗

Toward an understanding of violence: neurobehavioral aspects of unwarranted physical aggression: Aspen Neurobehavioral Conference consensus statement.

OBJECTIVE: Violence is a global problem that poses a major challenge to individuals and society. This document is a consensus statement on neurobehavioral aspects of violence as one approach to its understanding and control. BACKGROUND: This consensus group was convened under the auspices of the Aspen Neurobehavioral Conference, an annual consensus conference devoted to the understanding of issues related to mind and brain. The conference is supported by the Brain Injury Association and by individual philanthropic contributions. Participants were selected by conference organizers to represent leading opinion in neurology, neuropsychology, psychiatry, trauma surgery, nursing, evolutionary psychology, medical ethics, and law. METHODS: A literature review of the role of the brain in violent behavior was conducted and combined with expert opinion from the group. The major goal was to survey this field so as to identify major areas of interest that could be targeted for further research. Additional review was secured from the other attendees at the Aspen Neurobehavioral Conference. RESULTS: The group met in the spring of 1998 and 1999 for two 5-day sessions, between which individual assignments were carried out. The consensus statement was prepared after the second meeting, and agreement on the statement was reached by participants after final review of the document. CONCLUSIONS: Violence can result from brain dysfunction, although social and evolutionary factors also contribute. Study of the neurobehavioral aspects of violence, particularly frontal lobe dysfunction, altered serotonin metabolism, and the influence of heredity, promises to lead to a deeper understanding of the causes and solution of this urgent problem.

Adult↗

Evolutionary and functional significance of two CYP19 genes differentially expressed in brain and ovary of goldfish.

Remarkably high levels of cytochrome P450 aromatase (P450arom) enzyme are expressed in the brains of teleost fish when compared to the ovaries of the same fish, or to the brain or ovaries of other vertebrates. Northern analysis using a full-length P450arom cDNA from a goldfish brain library indicates high accumulated levels of CYP19 mRNA in the brain but fails to detect P450arom mRNA in the ovary. The possibility of different brain and ovarian mRNA variants was investigated. Reverse transcription-polymerase chain reaction (RT-PCR) amplification of ovarian RNA using degenerate primers led to the isolation of a 243 bp P450arom cDNA fragment with approximately 20% of nucleotide and amino acid replacements when compared to the brain cDNA. Southern analysis with sequence-specific probes indicated two distinct CYP19 loci, and this was confirmed by PCR-restriction enzyme analysis of genomic DNA. Corresponding brain- and ovary-type genomic sequences were identified in a second, diploid fish species (zebrafish), evidence that two genes are not caused per se by tetraploidy in goldfish. RT-PCR analysis of different tissues with sequence-specific primers showed high levels of the brain mRNA variant and much lower levels of the ovarian variant in neural tissues with high enzyme activity. In contrast, the ovary expressed low levels of the ovarian mRNA variant exclusively. The data imply that the expression of two CYP19 genes in goldfish is controlled by distinct regulatory mechanisms. Further studies are required to determine whether the two genes lead to functionally distinct isozymes.

Amino Acid Sequence↗

Expression of engrailed in the developing brain and appendages of the onychophoran euperipatoides kanangrensis (Reid).

We have cloned an engrailed-class gene in the onychophoran Euperipatoides kanangrensis and investigated its expression using in situ hybridisation. The expression pattern was found to differ drastically from that previously described for another onychophoran species. In the present investigation, engrailed transcripts were detected in a subset of developing neurons in the brain anlage, and in the mesoderm as well as ectoderm of the developing limb buds. The engrailed positive cells of the brain are of differing developmental maturity, ranging from subepidermal neuronal precursors to neurons located basally in the embryo with developing axons. The lack of the traditional expression in the posterior compartment of segments reported earlier in onychophorans is discussed, and we suggest that onychophorans may have acquired two copies of engrailed with different functions.

Amino Acid Sequence↗

From variable to constant cell numbers: cellular characteristics of the arthropod nervous system argue against a sister-group relationship of Chelicerata and "Myriapoda" but favour the Mandibulata concept.

In the new debate on arthropod phylogeny, structure and development of the nervous system provide important arguments. The architecture of the brain of Hexapoda, Crustacea and Chelicerata in recent years has been thoroughly compared against an evolutionary background. However, comparative aspects of the nervous systems in these taxa at the cellular level have been examined in only a few studies. This review sets out to summarize these aspects and to analyse the existing data with respect to the concept of individually identifiable neurons. In particular, mechanisms of neurogenesis, the morphology of serotonergic interneurons, the number of motoneurons, and cellular features and development of the lateral eyes are discussed. We conclude that in comparison to the Mandibulata, in Chelicerata the numbers of neurons in the different classes examined are much higher and in many cases are not fixed but variable. The cell numbers in Mandibulata are lower and the majority of neurons are individually identifiable. The characters explored in this review are mapped onto an existing phylogram, as derived from brain architecture in which the Hexapoda are an in-group of the Crustacea, and there is not any conflict of the current data with such a phylogenetic position of the Hexapoda. Nevertheless, these characters argue against a sister-group relationship of "Myriapoda" and Chelicerata as has been recently suggested in several molecular studies, but instead provide strong evidence in favour of the Mandibulata concept.

Animals↗

Electrical potentials indicate stimulus expectancy in the brains of ants and bees.

In vertebrates, and in humans in particular, so-called 'omitted stimulus potentials' can be electrically recorded from the brain or scalp upon repeated stimulation with simple stimuli such as light flashes. While standard evoked potentials follow each stimulus in a series, 'omitted stimulus potentials' occur when an additional stimulus is expected after the end of a stimulus series. These potentials represent neuronal plasticity and are assumed to be involved in basic cognitive processes. We recorded electroretinograms from the eyes and visually evoked potentials from central brain areas of honey bees and ants, social insects to which cognitive abilities have been ascribed and whose rich-behavioral repertoires include navigation, learning and memory. We demonstrate that omitted stimulus potentials occur in these insects. Omitted stimulus potentials in bees and ants show similar temporal characteristics to those found in crayfish and vertebrates, suggesting that common mechanisms may underlie this form of short-term neuronal plasticity.

Animals↗