Evolutionary Divergence in Brain Size between Migratory and Resident Birds

Despite important recent progress in our understanding of brain evolution, controversy remains regarding the evolutionary forces that have driven its enormous diversification in size. Here, we report that in passerine birds, migratory species tend to have brains that are substantially smaller (relative to body size) than those of resident species, confirming and generalizing previous studies. Phylogenetic reconstructions based on Bayesian Markov chain methods suggest an evolutionary scenario in which some large brained tropical passerines that invaded more seasonal regions evolved migratory behavior and migration itself selected for smaller brain size. Selection for smaller brains in migratory birds may arise from the energetic and developmental costs associated with a highly mobile life cycle, a possibility that is supported by a path analysis. Nevertheless, an important fraction (over 68%) of the correlation between brain mass and migratory distance comes from a direct effect of migration on brain size, perhaps reflecting costs associated with cognitive functions that have become less necessary in migratory species. Overall, our results highlight the importance of retrospective analyses in identifying selective pressures that have shaped brain evolution, and indicate that when it comes to the brain, larger is not always better.     

Glycosaminoglycans as regulators of stem cell differentiation

ES (embryonic stem) cell differentiation is dependent on the presence of HS (heparan sulfate). We have demonstrated that, during differentiation, the evolution of specific cell lineages is associated with particular patterns of GAG (glycosaminoglycan) expression. For example, different HS epitopes are synthesized during neural or mesodermal lineage formation. Cell lines mutant for various components of the HS biosynthetic pathway are selectively impaired in their differentiation, with lineage-specific effects observed for some lines. We have also observed that the addition of soluble GAG saccharides to cells, with or without cell-surface HS, can influence the pace and outcome of differentiation, again highlighting specific pattern requirements for particular lineages. We are combining this work with ongoing studies into the design of artificial cell environments where we have optimized three-dimensional scaffolds, generated by electrospinning or by the formation of hydrogels, for the culture of ES cells. By permeating these scaffolds with defined GAG oligosaccharides, we intend to control the mechanical environment of the cells (via the scaffold architecture) as well as their biological signalling environment (using the oligosaccharides). We predict that this will allow us to control ES cell pluripotency and differentiation in a three-dimensional setting, allowing the generation of differentiated cell types for use in drug discovery/testing or in therapeutics.     

New magnetic resonance contrast agents as biochemical reporters

Magnetic resonance imaging is a noninvasive, volume rendering diagnostic technique that uses lanthanide complexes to enhance proton relaxation. Magnetic resonance imaging is not limited by light scattering as optical microscopic techniques are, and allows imaging of whole animals. Clinical contrast agents are nonspecific and report solely on anatomy, whereas contrast agents that can be activated can be tailored to report on the physiological status or metabolic activity of biological systems. These new classes of magnetic resonance contrast agents represent a substantial leap in the type of information that can be derived from imaging experiments, and are the focus of this review.     

Structure-function relationships in heparin cofactor II: spectral analysis of aromatic residues and absence of a role for sulfhydryl groups in thrombin inhibition

This study characterizes the structural and functional significance of sulfhydryl residues in human plasma heparin cofactor II (HCII). For quantification of sulfhydryl groups, the extinction coefficient of HCII was redetermined and found to be 0.593 ml mg-1 cm-1 using second-derivative spectroscopy and multicomponent analysis assuming 4, 10, and 2 residues of tryptophan, tyrosine, and tyrosine-O-sulfate per mole of protein, respectively. The results show that tyrosine-O-sulfate residues in HCII and in cholecystokinin peptide fragments (as model compounds) do not significantly contribute to the absorbance spectrum from 280 to 300 nm. A total of three sulfhydryl groups per mole of HCII was detected by Ellman's reagent titration, with or without treatment with dithioerythritol, indicating the absence of intramolecular disulfide bonds. Incubation of HCII with 0.1-10 mM dithioerythritol did not diminish its heparin-enhanced thrombin inhibition activity. Treatment with various sulfhydryl-specific reagents, including p-mercuribenzoate, HgCl2, and N-substituted maleimide derivatives, inactivated HCII. Titration with Ellman's reagent after these reactions identified the modification site as a cysteinyl residue(s). However, complete methanethio derivatization of the sulfhydryl groups of HCII using methyl methanethiosulfonate did not alter heparin-catalyzed thrombin inhibition. These results indicate that the sulfhydryl groups of HCII are not essential for thrombin inhibition. HCII differs from antithrombin III, which contains an essential disulfide bond for heparin-dependent thrombin inhibition (Longas, M. O., et al. (1980) J. Biol. Chem. 255, 3436). Furthermore, within the "serpin" (serine proteinase inhibitor) superfamily, HCII resembles chicken ovalbumin in occurrence of sulfhydryl residues and reactivity with various sulfhydryl group-directed compounds.     

Plasma and erythrocyte membrane long chain polyunsaturated fatty acids in endogenous depression

Patients suffering from endogenous depression had significantly greater proportions of long chain polyunsaturated fatty acids (LCP), docosahexaenoic acid (22:6ω3) and eicosapentaenoic acid (20:5ω3), and a reduced proportion of linoleic acid (18:2ω6) in their plasma choline phosphoglycerides (CPG) compared with age-sex-matched healthy controls. Patients suffering from reactive depression or from other psychiatric disorders did not differ significantly from matched controls. Changes in the fatty acid composition of the major erythrocyte membrane phospholipids were in the same direction but were less marked. The importance and possible reasons for the elevated LCP in endogenous depression are discussed.     

Relation of fetal and infant growth to plasma fibrinogen and factor VII concentrations in adult life.

OBJECTIVE--To determine whether reduced fetal and infant growth are associated with higher plasma fibrinogen and factor VII concentrations in adult life. DESIGN--Follow up study of men born during 1920-30 whose weights at birth and at 1 year had been recorded by health visitors, and men born during 1935-43 whose size at birth had been measured in detail. SETTING--Hertfordshire and Preston, England. SUBJECTS--591 men born in east Hertfordshire who still lived there and 148 men born in Preston who still lived in or close to the city. MAIN OUTCOME MEASURES--Plasma fibrinogen and factor VII concentrations. RESULTS--Among men in Hertfordshire mean plasma fibrinogen and factor VII concentrations fell with increasing weight at 1 year (from 3.21 g/l in men of less than or equal to 18 lb to 2.93 g/l in men greater than or equal to 27 lb and from 122% of standard to 103%; p less than 0.001, p less than 0.005 respectively). The trends were independent of cigarette smoking, alcohol consumption, body mass index, and social class. Neither plasma fibrinogen nor factor VII concentration was related to birth weight. In men in Preston, however, fibrinogen concentration fell progressively as the ratio of placental weight to birth weight decreased (p = 0.01). CONCLUSIONS--Reduced growth in fetal life and infancy is strongly related to high plasma concentrations of the haemostatic factors fibrinogen and factor VII. This may be a persisting response to impaired liver development during a critical early period.     

Fibrinogen: a possible link between social class and coronary heart disease.

Mortality from coronary heart disease in civil servants in the lowest grade of employment has been found to be about three times that of men in the highest grade of employment. As part of an investigation of this finding several haemostatic variables were measured in a sample of 29 men in lower grades of employment and 45 men in higher grades. There was a significant difference in plasma fibrinogen concentrations between men in lower grades of employment and those in higher grades (mean 3.39 g/l v 2.95 g/l, respectively; p less than 0.01) but not in other haemostatic variables. Multiple regression analyses showed significant independent associations of fibrinogen concentration with smoking (p less than 0.05) and grade of employment (p less than 0.05). The size of the observed difference between the grades of employment was similar to that between those dying of coronary heart disease or surviving during longitudinal study; it may therefore be an important part of the mechanism underlying social class differences in coronary heart disease. The statistical relation between fibrinogen concentrations and other characteristics that may be concerned in the aetiology of coronary heart disease was examined. A summary measure of job stress was significantly related to fibrinogen concentration (p less than 0.01) and made a substantial contribution to explaining the differences between grades of employment. Behaviour type and a score of physical activity were not significantly related to fibrinogen concentration.