A long term trend in tooth size in the Eastern Mediterranean

Although estimates of brain weight are useless in prediction of individual intelligence in man, the available data (none of them entirely adequate) suggest that the real correlation may be as high as 0.3. Evaluation of causes suggests the participation of a direct effect. Natural selection on intelligence at a current estimated intensity suffices to explain the rapid rate of increase of brain size in human evolution. Selection on birth weight may also suffice for this. It does not seem overly difficult to estimate directly the relationships among brain weight, intelligence, and fitness.     

Newborn Brain: Body weight ratios.

Newborn brain:body weight ratios are generally considered to be constant in man. In autopsy studies many factors influence the measured weight of the brain, and therefore the conclusions based on such observations, including the gestational age of the material, the presence or absence of intrauterine growth retardation, and the cause of death. In this study these influences have been eliminated by careful selection of normally grown fullterm newborns not subject to the factors influencing brain weight. Using double logarithmic plots, brain size in fullterm newborns is found to be related to the 0.64 power of birth weight. There is a negative correlation between relative brain size and increasing fullterm birth size in man.     

Allomaternal care, life history and brain size evolution in mammals

Humans stand out among the apes by having both an extremely large brain and a relatively high reproductive output, which has been proposed to be a consequence of cooperative breeding. Here, we test for general correlates of allomaternal care in a broad sample of 445 mammal species, by examining life history traits, brain size, and different helping behaviors, such as provisioning, carrying, huddling or protecting the offspring and the mother. As predicted from an energetic-cost perspective, a positive correlation between brain size and the amount of help by non-mothers is found among mammalian clades as a whole and within most groups, especially carnivores, with the notable exception of primates. In the latter group, the presence of energy subsidies during breeding instead resulted in increased fertility, up to the extreme of twinning in callitrichids, as well as a more altricial state at birth. In conclusion, humans exhibit a combination of the pattern found in provisioning carnivores, and the enhanced fertility shown by cooperatively breeding primates. Our comparative results provide support for the notion that cooperative breeding allowed early humans to sidestep the generally existing trade-off between brain size and reproductive output, and suggest an alternative explanation to the controversial ‘obstetrical dilemma’-argument for the relatively altricial state of human neonates at birth.     

Brain size at birth throughout human evolution: a new method for estimating neonatal brain size in hominins

An increase in brain size is a hallmark of human evolution. Questions regarding the evolution of brain development and obstetric constraints in the human lineage can be addressed with accurate estimates of the size of the brain at birth in hominins. Previous estimates of brain size at birth in fossil hominins have been calculated from regressions of neonatal body or brain mass to adult body mass, but this approach is problematic for two reasons: modern humans are outliers for these regressions, and hominin adult body masses are difficult to estimate. To accurately estimate the brain size at birth in extinct human ancestors, an equation is needed for which modern humans fit the anthropoid regression and one in which the hominin variable entered into the regression equation has limited error. Using phylogenetically sensitive statistics, a resampling approach, and brain-mass data from the literature and from National Primate Research Centers on 362 neonates and 2802 adults from eight different anthropoid species, we found that the size of the adult brain can strongly predict the size of the neonatal brain (r² = 0.97). This regression predicts human brain size, indicating that humans have precisely the brain size expected as an adult given the size of the brain at birth. We estimated the size of the neonatal brain in fossil hominins from a reduced major axis regression equation using published cranial capacities of 89 adult fossil crania. We suggest that australopiths gave birth to infants with cranial capacities that were on average 180 cc (95% CI: 158–205 cc), slightly larger than the average neonatal brain size of chimpanzees. Neonatal brain size increased in early Homo to 225 cc (95% CI: 198–257 cc) and in Homo erectus to approximately 270 cc (95% CI: 237–310 cc). These results have implications for interpreting the evolution of the birth process and brain development in all hominins from the australopiths and early Homo, through H. erectus, to Homo sapiens.     

Transglutaminase Activity in Rat Brain: Characterization, Distribution, and Changes with Age

The activity of transglutaminase was characterized in the rat brain. In adults, comparable levels of transglutaminase activity are present in all brain regions examined. The activity is present in all subcellular fractions, as studied by differential centrifugation, but the soluble fraction contains the highest specific activity. The endogenous activity (enzyme activity assayed in the absence of the exogenous substrate casein) is very low in all subcellular fractions, except in the synaptosomal fraction where its highest levels are about 40-60% of the activity assayed in the presence of casein. Furthermore, enzyme activity is present on the external surface of synaptosomes. In the soluble fraction, maximal activity can be detected between pH values of 9 and 10 when assayed in the presence of 5 mM CaCl2 (with half-maximal activity requiring 0.75 mM CaCl2) and 0.4 mM putrescine (with an apparent Km for putrescine of 0.1 mM). The activity can be partially inhibited by ZnCl2 (with an IC50 of 4.5 mM) and by AlCl3 (with an IC50 of 5.1 mM). In the cerebellum, where the full span of neuronal development can be studied after birth, the highest specific activity is observed just after birth, thereafter the activity starts to decline and by 14 days, after a reduction of about 65%, it reaches levels observed throughout life.     

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.     

Human Brain-Type Glycogen Phosphorylase: Quantitative Localization in Human Tissues Determined with an Immunoassay System

Abstract: Glycogen phosphorylase (EC 2.4.1.1) from human brain tissue was purified to homogeneity. Antisera were developed in rabbits with purified phosphorylase as the immunogen. Antibodies were first affinity-purified with a column of brain phosphorylase-coupled Sepharose, and then the antibody fraction was adsorbed with a column of muscle phosphorylase-coupled Sepharose to remove antibodies reactive also with muscle phosphorylase. By using the specific antibodies, a sandwich-type immunoassay system for measurement of brain phosphorylase was prepared. The assay system consisted of polystyrene balls with immobilized antibrain phosphorylase F(ab')₂ fragments and the same antibody Fab' fragments labeled with β-D-galactosidase from Escherichia coli. The assay was sensitive and specific to the brain phosphorylase. The minimum detection limit of the assay was 0.1 ng/assay tube, and the cross-reactivity of the assay with muscle phosphorylase was <1%. Tissue concentrations of immunoreactive brain-type phosphorylase were estimated. The phosphorylase was present in the heart at as high a level as in the brain. The immunoreactivity for brain phosphorylase was distributed widely at a significant concentration in various peripheral tissues, such as the digestive tract, bladder, aorta, liver, and testis. Immunohistochemical localization of brain phosphorylase in the CNS revealed that the enzyme is present in most astrocytes and amyloid bodies, as well as in some neurons in the cerebral cortex and Golgi cells in the cerebellar cortex.     

Curvilinear, geometric and phylogenetic modeling of basicranial flexion: is it adaptive, is it constrained?

Prior work has shown that the degree of basicranial flexion among primates is determined by relative brain size, with anatomically modern humans possibly having a less flexed basicranium than expected for their relative brain size. Basicranial flexion has also been suggested to be adaptive in that it maintains a spheroid brain shape, thereby minimizing connections between different parts of the brain. In addition, it has been argued that the degree of flexion might be constrained such that increases in relative brain size beyond that seen in Australopithecus africanus were accommodated by mechanisms other than basicranial flexion. These hypotheses were evaluated by collating an extensive data set on basicranial flexion and relative brain size in primates and other mammals. The data were analyzed using standard least squares regression, geometric and curvilinear modeling, and phylogenetically independent contrasts (PICs). Geometric modeling does not support the hypothesis that flexion is an adaptation that facilitates enlargement of a spheroid brain. Whether humans have a less flexed basicranium than expected for their relative brain size depends on the phylogenetic vantage point from which it is evaluated. They are as flexed as expected for a descendant of the last common ancestor of the Paranthropus-Homo clade, but their degree of flexion cannot be predicted from the basal hominoid node, even if their relative brain size is specified. Humans undoubtedly occupy an unusual part of morphospace in terms of basicranial flexion and relative brain size, but this does not mean that their degree of flexion is or is not constrained. Curvilinear regression models and standard linear regression models describe the relationship between flexion and relative brain size equally well. Hypotheses that the degree of flexion is or is not constrained cannot be discriminated at present. Consideration of recently published ontogenetic data in the context of the interspecific data for adults suggests that much of the variance in basicranial flexion can still be explained as a mechanical consequence of brain enlargement relative to basicranial length.     

Development of human brain

The human has the most complex brain of the primates group. Their development is prolonged beyond birth and it is not completed structurally nor neurochemically until age of 20 years. Decades later, degenerative phenomena begin to be evident, that little by little will drive us to death. At the end of the life, 113 grams aproximate of cerebral mass are lost. The endowment of furrows and convolutions are fixed before birth, while the cerebral surface ends up having values next to the adult at 2 years. However the cerebral weight reaches its maximum at the 20 year-old decade. A first phase of neuronal death appears during the prenatal life, which is continued by another postnatal phase, and it ends with the definitive number of neurons. However, along life, the number of neurons decreases little by little at the time of the neuroglial cells increase. Much about brain knowledge at the moment is difficult to apply to the cranial endocasts, although approaches from the MNR are hopeful.     

Therapeutic effect of erythropoietin on brain injury in premature mice with intrauterine infection

ObjectiveThe objective of this study is to explore the protective effect of erythropoietin (EPO) on brain injury induced by intrauterine infection in premature infants and its related mechanism, so as to provide reference for clinical medication.MethodsIntrauterine infection model is established by injecting lipopolysaccharide into pregnant mice, and HE staining of mouse placenta is used to judge whether the model of intrauterine infection is successful or not. Fifteen female rats are successfully pregnant and divided into intrauterine infection group (10 rats) and control group (5 rats). The mice in the intrauterine infection group are intraperitoneally injected with lipopolysaccharide (LPS) at a dose of 0.3 mg/kg. After delivery, 16 newborn mice in the control group are randomly selected as blank control group. 32 newborn mice in the intrauterine infection group are selected as model group, and then divided into infection group and EPO treatment group, 16 mice in each group. After birth, mice in the blank control group are intraperitoneally injected with 0.2 mL saline daily. The infected mice are intraperitoneally injected with 0.2 mL saline daily. The mice in the EPO treatment group are intraperitoneally injected with recombinant human erythropoietin (rhEPO) 5000 IU/kg daily. HE staining results, EPOR protein and NMDAR1 mRNA expression in brain tissue of three groups of neonatal mice were compared.ResultsFirstly, the blood vessels of the mice in the intrauterine infection group are markedly hyperemic and edematous, and the infiltration of neutrophils is increased. The white matter structure of the neonatal mice in the intrauterine infection group is loose and stained lightly. The nerve fibers in the brain are different in thickness and disordered in arrangement. The nucleus is small and dark stained. The number of glial cells in brain tissue increases significantly. Secondly, the EPOR protein expression and physiological level of neonatal mice in intrauterine infection group increase significantly at 3, 7 and 14 days after birth. Compared with the blank control group, the difference is statistically significant (P < 0.05). On the 3rd day after birth, the expression level of EPOR protein in the EPO treated group is significantly higher than that in the intrauterine infection group (P < 0.05). Thirdly, the expression level of NMDA R1mRNA in brain tissue of neonatal mice at birth, on the 3rd and 7th day after EPO treatment is significantly lower than that of intrauterine infection group (P < 0.05).ConclusionEPO can promote the proliferation and differentiation of brain endogenous neural stem cells, and has a certain therapeutic effect on brain injury of premature mice caused by intrauterine infection.     

Cholesterol Esters of the Human Brain During Fetal and Early Postnatal Development: Content and Fatty Acid Composition

Abstract: The content and fatty acid composition of cholesterol esters of the human brain during development from 13 weeks' gestation up to 26 months of age was studied. The three major brain areas, the forebrain, cerebellum, and the brain stem, were studied separately. The concentration of the esters in each brain region was the highest at the earliest fetal age of 13 weeks and fell during growth. However, transient rises in the concentration were observed, at about birth in the forebrain and at 4–5 months after birth in the cerebellum The peak concentration during the transient period (125–150 μg/g fresh tissue of forebrain and 100–125 μg/g of cerebellum) was similar to the concentrations observed in the two parts respectively during early fetal ages. The brain stem also showed similar transient peak at about a few weeks before birth, but only when the esters were expressed as amount per cell. In absolute terms, a clear transient period was evident in the forebrain between birth and 9 months, while in the cerebellum or the brain stem, the total amount of the esters increased up to about 1 year of age and then remained almost unchanged. The major fatty acids of the esters were palmitic, palmitoleic, stearic, oleic, linoleic and arachidonic acid. Most of these fatty acids showed certain changes in relative proportions during development. Thus, in the forebrain, palmitic and oleic acid decreased from about 32% and 40% (weight percentages) at 13–15 weeks of gestation to about 20% and 25% respectively at 26 months of age. During this period, linoleic and arachidonic acid increased from about 3% and S% to about 10% and 24%, respectively. Most of these changes occurred after birth. The cerebellum and the brain stem differed only slightly from the forebrain in either the fatty acid composition or the pattern of the developmental changes in the composition.     

Changes in free fatty acids and diglycerides in mouse brain at birth and during anoxia

Abstract: Within the first few hours of life in the mouse, marked changes were seen in brain endogenous free fatty acids (FFA). A 21% decrease in the total FFA pool occurred during the 1st h of life, and a constant value was maintained thereafter to 10 h. Polyunsaturated fatty acids displayed a different pattern of change. There was 27% less free ararhidonic acid at birth (0 h) than 1 h later. Similar values were obtained for docosahexaenoic acid at birth and at 10 h, although palmitoleic and oleic acids decreased markedly after 1 h. The polyunsaturated fatty acyl chains of diglycerides (DG) showed a statistically significant increase as a function of time after birth, despite an unchanged total DG pool size. The brains of pups subjected to 40 min of N₂-anoxia immediately after delivery exhibited a decrease in FFA, especially the monoenoic components, but 60 min of anoxia yielded higher FFA levels. Anoxia induced at 10 h increased FFA and arachidonic acid was higher than when anoxia was induced at 0 h. FFA accumulation was further stimulated by raising the environmental temperature during anoxia. When anoxia was induced, DG exhibited a net increase in palmitate, oleate, and palmitoleate at 0 and 10 h. No arachidonoyl-DG accumulated at 0 h, even after 60 min of anoxia, and stearate was unchanged at 0 and 10 h. The lipid changes observed in the brain during the first hours of life suggest that the enzymatic reactions that promote accumulation of free arachidonic and docosahexaenoic acids and arachidonoyl-DG in the mature brain are present at low levels at the time of delivery. The sluggish modifications found in our study may be related to the longer resistance of newborns to oxygen deficiency.     

Developmental Change in the Glycosaminoglycan Composition of the Rat Brain

Abstract: Glycosaminoglycans (GAGs) were isolated from the brains of pre- and postnatal rats. The GAG content of the brain, based on the amount of DNA, was constant during the period from day 13 to day 15 of gestation. After day 15, the GAG content began to increase and reached a plateau by 10 days after birth. Hyaluronate (HA) was the main GAG (> 60% of the total) in the fetal rat brain, and the relative amount of HA decreased after birth. Conversely, the relative amount of chondroitin sulfate increased with development and reached the adult level by 20 days after birth. Heparan sulfate (HS) was the major sulfated GAG in the fetal rat brain at early developmental stages, but HS accounted for approximately 10% of the total GAG in the postnatal brains. In addition to these GAGs, a polysialosyl glycoconjugate was isolated from rapidly growing brains of the rat. These three GAGs could be isolated either from the cerebellum, cerebrum, or brainstem of the newborn rat. A closely similar age-related change in the GAG composition was observed in each of these different regions of the brain. The developmental change could be implicated in morphogenesis or maturation of the brain.     

Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings

Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder. It is characterized by two principal features, microcephaly present at birth and nonprogressive mental retardation. The microcephaly is the consequence of a small but architecturally normal brain, and it is the cerebral cortex that shows the greatest size reduction. There are at least seven MCPH loci, and four of the genes have been identified: MCPH1, encoding Microcephalin; MCPH3, encoding CDK5RAP2; MCPH5, encoding ASPM; and MCPH6, encoding CENPJ. These findings are starting to have an impact on the clinical management of families affected with MCPH. Present data suggest that MCPH is the consequence of deficient neurogenesis within the neurogenic epithelium. Evolutionary interest in MCPH has been sparked by the suggestion that changes in the MCPH genes might also be responsible for the increase in brain size during human evolution. Indeed, evolutionary analyses of Microcephalin and ASPM reveal evidence for positive selection during human and great ape evolution. So an understanding of this rare genetic disorder may offer us significant insights into neurogenic mitosis and the evolution of the most striking differences between us and our closest living relatives: brain size and cognitive ability.     

Endocranial volumes of primate species: scaling analyses using a comprehensive and reliable data set

We present a compilation of endocranial volumes (ECV) for 176 non-human primate species based on individual data collected from 3813 museum specimens, at least 88% being wild-caught. In combination with body mass data from wild individuals, strong correlations between endocranial volume and body mass within taxonomic groups were found. Errors attributable to different techniques for measuring cranial capacity were negligible and unbiased. The overall slopes for regressions of log ECV on log body mass in primates are 0.773 for least-squares regression and 0.793 for reduced major axis regression. The least-squares slope is reduced to 0.565 when independent contrasts are substituted for species means (branch lengths from molecular studies). A common slope of 0.646 is obtained with logged species means when grade shifts between major groups are taken into account using ANCOVA. In addition to providing a comprehensive and reliable database for comparative analyses of primate brain size, we show that the scaling relationship between brain mass and ECV does not differ significantly from isometry in primates. We also demonstrate that ECV does not differ substantially between captive and wild samples of the same species. ECV may be a more reliable indicator of brain size than brain mass, because considerably larger samples can be collected to better represent the full range of intraspecific variation. We also provide support for the maternal energy hypothesis by showing that basal metabolic rate (BMR) and gestation period are both positively correlated with brain size in primates, after controlling for the influence of body mass and potential effects of phylogenetic relatedness.     

Identification with a Monoclonal Antibody of a Phylogenetically Conserved Brain-Specific Determinant on a 130,000 Molecular Weight Glycoprotein of Human Brain

Human brain glycoproteins depleted of Thy-1 antigen were used to immunise Balb/c mice for monoclonal antibody production. The F3-87-8 antibody described in this paper interacts with a determinant present in large amounts on all human brain subregions studied (cerebral cortical grey matter, white matter, caudate, thalamus, dentate nucleus, putamen, cerebellar cortex) but absent from all other tissues examined (liver, heart, kidney, spleen, thymus, lymph node, erythrocyte, adrenal gland, and peripheral nerve). The determinant is conserved in mammalian evolution, as the brains of the rat and dog have amounts equal to that found in human brain. Balb/c mouse brain has approximately one-third as much antigen activity as these other mammalian brains, whereas brains of the frog and chicken have no detectable antigenic activity. Developmental studies showed that 16-week human foetal brain and neonatal dog brain had little or no antigen activity, indicating a dramatic increase in the amount of the determinant with brain maturation. Biochemical studies showed that the F3-87-8-bearing molecule was a major sialoglycoprotein of human brain with an apparent molecular weight of 130,000. It was shown by immunofluorescence to be particularly localised in what appeared to be fibre tracts in the thalamus and basal ganglia, and in the dentate nucleus, although all regions including grey matter were stained.     

Life history costs and benefits of encephalization: a comparative test using data from long-term studies of primates in the wild

The correlation between brain size and life history has been investigated in many previous studies, and several viable explanations have been proposed. However, the results of these studies are often at odds, causing uncertainties about whether these two character complexes underwent correlated evolution. These disparities could arise from the mixture of wild and captive values in the datasets, potentially obscuring real relationships, and from differences in the methods of controlling for phylogenetic non independence of species values. This paper seeks to resolve these difficulties by (1) proposing an overarching hypothesis that encompasses many of the previously proposed hypotheses, and (2) testing the predictions of this hypothesis using rigorously compiled data and utilizing multiple methods of analysis. We hypothesize that the adaptive benefit of increased encephalization is an increase in reproductive lifespan or efficiency, which must be sufficient to outweigh the costs due to growing and maturing the larger brain. These costs and benefits are directly reflected in the length of life history stages. We tested this hypothesis on a wide range of primate species. Our results demonstrate that encephalization is significantly correlated with prolongation of all stages of developmental life history except the lactational period, and is significantly correlated with an extension of the reproductive lifespan. These results support the contention that the link between brain size and life history is caused by a balance between the costs of growing a brain and the survival benefits the brain provides. Thus, our results suggest that the evolution of prolonged life history during human evolution is caused by increased encephalization.     

The allometric approach to species differences in brain size

Allometric methods can be used to test quantitative theories of the relationship between brain size and body size across species, and to search for ecological, behavioural, life history, and ontogenetic correlates of brain size. Brain size scales with an allometric exponent of around 0.75 against body size across mammals, but is closer to 0.56 for birds and for reptiles. The slope of the allometric line often varies depending upon the taxonomic level of analysis. However, this phenomenon, at least in mammals, may be a statistical artifact. Brain size for a given body size (relative brain size) varies among orders in birds and mammals, and some dietary associations with relative brain size have been found in particular taxa. Developmental status at birth is the most consistent correlate of relative brain size: precocial neonates have larger brains for a given maternal size than altricial neonates in both birds and mammals. Altricial neonates, however, have more brain growth following birth, and in birds also have larger relative adult brain sizes. Energetic explanations for differences in neonatal brain growth, although attractive on theoretical grounds, have largely failed to stand up to empirical tests.     

Large brains buffer energetic effects of seasonal habitats in catarrhine primates

Ecological factors have been shown to be important for brain size evolution. In this comparative study among catarrhine primates, we examine two different ways in which seasonality may be related to brain size. First, seasonality may impose energetic constraints on the brain because it forces animals to deal with periods of food scarcity (Expensive Brain hypothesis). Second, seasonality may act as a selective pressure to increase brain size, as behavioral flexibility helps to overcome periods of food scarcity (Cognitive Buffer hypothesis). Controlling for phylogeny, we found a strong negative relationship between brain size (relative to body mass) and the degree of experienced seasonality, as estimated by the variation in net energy intake. However, we also found a significant positive relationship between relative brain size and the effect of so-called cognitive buffering, proxied by the difference between environmental seasonality and the seasonality in net energy intake actually experienced by the animals. These results show that both energetic constraints of seasonal habitats as well as cognitive buffering affect brain size evolution, leaving environmental seasonality uncorrelated to brain size. With this study we show the importance of simultaneously considering both costs and benefits in models of brain size evolution.