Effects of adrenoceptor blockade on cardiac hypertrophy and myocardial phospholipids.

Catecholamines have been proposed as a stimulus for the hypertrophic response to pressure overload of the heart and could also mediate the membrane lipid changes associated with cardiac hypertrophy. To address both of these possibilities, cardiac hypertrophy was induced by aortic constriction in the presence or absence of chronic alpha- or beta-adrenoceptor blockade. Heart weights and heart weight to body weight ratios in aortic-constricted rats of the adrenoceptor-blocked and vehicle-treated groups were elevated to the same extent when compared with values in sham-operated rats of each group. Analysis of the fatty acyl composition of the major phospholipid classes revealed that similar changes occurred in vehicle-treated, alpha-blocked, and beta-blocked aortic-constricted rats when compared with respective groups of sham-operated rats. Specifically, linoleic acid was reduced in the phosphatidylcholine, phosphatidylethanolamine (PE), and cardiolipin (CL) fractions in all groups of aortic-constricted rats. This reduction was accompanied by increased docosahexaenoic acid, arachidonic acid, or palmitic acid in phosphatidylcholine; docosahexaenoic acid in phosphatidylethanolamine; and oleic acid in cardiolipin fractions. Adrenoceptor blockade did not prevent or attenuate the major changes in the fatty acyl composition of phospholipids or the increase in heart weight associated with aortic constriction. This suggests that a change in the level of adrenoceptor stimulation is not the stimulus for cardiac hypertrophy or the observed alterations in phospholipid composition in the pressure-overloaded rat heart.     

Odontometric microdifferentiation of transplanted Mexican Indian populations: Cuanalan and Saltillo

This study documents odontometric variation in four populations of related genetic background. It is found that the transplanted populations of Cuanalan and Saltillo have undergone significant microdifferentiation in tooth size relative to the two home valley populations. The extent and direction of this microdifferentiation is seen as reflecting differential amounts of admixture from African and European sources in demographic subunits of the two transplanted populations. The dental variables found to discriminate significantly between populations are the same variables predicted to be evolutionarily labile by Butler's Field Theory. Principal component analysis confirms the presence of morphological fields in these data and supports the position that each class has a stable tooth, with stability decreasing with increasing distance from the key tooth. The importance of hybridization in determining which variables significantly discriminate between populations is confounded by the effects of development of the dentition in morphogenetic fields. These data suggest the odontometric data provide an adequate, if somewhat conservative, base from which to evaluate microdifferentiation of human populations.     

Dynamic changes in optic fiber terminal arbors lead to retinotopic map formation: an in vivo confocal microscopic study

Dynamic remodeling of retinal ganglion cell terminal arbors has been proposed to contribute to formation of the topographically ordered retinotectal projection. To test this directly, the growth of individual terminal arbors was observed in live X. laevis tadpoles using a confocal microscope to visualize their complex three-dimensional structure. During initial development, nasal and temporal retinal arbors covered overlapping tectal areas. Despite subsequent remodeling, the dimensions and positions of the temporal arbors remained relatively stable. In contrast, the nasal arbors grew caudally, as they extended caudal branches and retracted rostral branches. These results suggest that differences in the remodeling of the nasal and temporal arbors lead to the emergence of retino-topography along the rostrocaudal axis of the tectum. All the terminal arbors were dynamic, including those with stable dimensions, suggesting that continual remodeling of arbors may be a universal feature of neuronal projections.     

Differences in the gastrointestinal microbiota of specific pathogen free mice: an often unknown variable in biomedical research

Large differences were found in the numbers of facultatively anaerobic Gram-negative bacteria in the gastrointestinal tract of mice from 3 major specific pathogen free (SPF) units in Australia. The species isolated also differed between mouse colonies. In one unit the presence of Enterobacter cloacae was found to dramatically influence the survival of mice following total body irradiation. This finding conforms with previous studies which have shown the influence of variation in gastrointestinal microbiota on the immune system and on susceptibility to infection. Given that the presence or absence of Enterobacteriaceae in the intestines of mice under investigation may influence experimental results, researchers using SPF rodents are encouraged to determine the baseline loading of these bacteria in their animals. Where results of immunological or irradiation studies from different colonies are likely to be compared, the enterobacterial status of the colony being used should be reported.     

The trk tyrosine protein kinase mediates the mitogenic properties of nerve growth factor and neurotrophin-3.

The product of the trk proto-oncogene encodes a receptor for nerve growth factor (NGF). Here we show that NGF is a powerful mitogen that can induce resting NIH 3T3 cells to enter S phase, grow in semisolid medium, and become morphologically transformed. These mitogenic effects are absolutely dependent on expression of gp140trk receptors, but do not require the presence of the previously described low affinity NGF receptor. gp140trk also serves as a receptor for the related factor neurotrophin-3 (NT-3), but not for brain-derived neurotrophic factor. Both NGF and NT-3 induce the rapid phosphorylation of gp140trk receptors and the transient expression of c-Fos proteins. However, NT-3 appears to elicit more limited mitogenic responses than NGF. These results indicate that the product of the trk proto-oncogene is sufficient to mediate signal transduction processes induced by NGF and NT-3, at least in proliferating cells.     

The trk proto-oncogene encodes a receptor for nerve growth factor.

Two classes of receptors with distinct affinities for nerve growth factor (NGF) have been identified. The low affinity receptor (Kd approximately 10(-9) to 10(-8) M) is a cysteine-rich glycoprotein encoded by the previously characterized LNGFR gene. The structural nature of the high affinity receptor (Kd approximately 10(-11) to 10(-10) M) has yet to be established. In this study we show that the product of the human trk proto-oncogene (gp140trk) binds NGF with high affinity. Moreover, NGF could be chemically cross-linked to the endogenous gp140trk present in rat PC12 pheochromocytoma cells as well as to gp140trk ectopically expressed in mouse fibroblasts and in insect Sf9 cells. High affinity binding of NGF to gp140trk can occur in the absence of low affinity LNGFR receptors, at least in nonneural cells. Addition of NGF to PC12 cells elicits rapid phosphorylation of gp140trk on tyrosine residues and stimulates its tyrosine kinase activity. These results indicate that gp140trk is a functional NGF receptor that mediates at least some of the signal transduction processes initiated by this neurotrophic factor.     

Mapping of epitopes for monoclonal antibodies against human platelet thrombospondin with electron microscopy and high sensitivity amino acid sequencing

A panel of monoclonal antibodies (Mab's) has been raised against human platelet thrombospondin (TSP). One Mab, designated A2.5, inhibits the hemagglutinating activity of TSP and immunoprecipitates the NH2 terminal 25 kD heparin binding domain of TSP (Dixit, V.M., D. M. Haverstick, K. M. O'Rourke, S. W. Hennessy, G. A. Grant, S. A. Santoro, and W. A. Frazier, 1985, Biochemistry, in press). Another Mab, C6.7, blocks the thrombin-stimulated aggregation of live platelets and immunoprecipitates an 18-kD fragment distinct from the heparin binding domain (Dixit, V. M., D. M. Haverstick, K. M. O'Rourke, S. W. Hennessy, G. A. Grant, S. A. Santoro, and W. A. Frazier, 1985, Proc. Natl. Acad. Sci. 82: 3472-3476). To determine the relative locations of the epitopes for these Mabs in the three-dimensional structure of TSP, we have examined TSP-Mab complexes by electron microscopy of rotary-shadowed proteins. The TSP molecule is composed of three 180-kD subunits, each of which consists of a small globular domain (approximately 8 nm diam) and a larger globular domain (approximately 16 nm diam) connected by a thin, flexible strand. The subunit interaction site is on the thin connecting strands, nearer the small globular domains. Mab A2.5 binds to the cluster of three small domains, indicating that this region contains the heparin binding domain and thus represents the NH2 termini of the TSP peptide chains. Mab C6.7 binds to the large globular domains on the side opposite the point at which the connecting strand enters the domain, essentially the maximum possible distance from the A2.5 epitope. Using high sensitivity automated NH2 terminal sequencing of TSP chymotryptic peptides we have ordered these fragments within the TSP peptide chain and have confirmed that the epitope for C6.7 in fact lies near the extreme COOH terminus of the peptide chain. In combination with other data, we have been able to construct a map of the linear order of the identified domains of TSP that indicates that to a large extent, the domains are arranged co-linearly with the peptide chain.     

Yield responses of crops to changes in environment and management practices: Model sensitivity analysis. I. Maize

YIELD, a parametric crop production model, employs climatic data to calculate actual and potential yield for various crops and includes formulations for specific crop and growth stage effects. The objective was to demonstrate the sensitivity of YIELD for grain corn (maize) to changes in various environmental and decision-making inputs. Five temperature, five solar radiation, six relative humidity regimes, five water application schemes, and four irrigation frequencies were included in this study. The effects of different soil types and wind regimes on crop water requirements were investigated. The model output includes crop yield, water use efficiency, and management efficiency. Among the results, yield decreased on the average by 3.9% per one degree (C) increase in air temperature. A 1% change in solar radiation resulted in an average of 1% change in yield. Similar changes in relative humidity caused a yield change of about 0.8%.     

BIOCHEMICAL HETEROZYGOSITY AND MORPHOLOGIC VARIATION IN A COLONY OF PAPIO HAMADRYAS HAMADRYAS BABOONS

This analysis examines the association between genetic heterozygosity and individual morphologic variation in a captive population of Papio hamadryas hamadryas consisting of 403 juveniles and adults. The population structure of the colony was artificially generated and maintained and is thus rigorously defined. Subpopulations delimited by age, sex, and degree of inbreeding are also explored. Heterozygosity, as enumerated from six simple Mendelian biochemical loci, is compared with the residual morphologic variation of each individual for each of 20 quantitative traits. Use of a sequential Bonferroni technique nullifies all significant correlations. Principal-components analysis reduces the morphometrics to a single or few significant axes in each population. The first axis of the total population contains 86.07% of the variation in the sample and the absolute values of the factor scores exhibit a significant positive correlation with heterozygosity at P < 0.05. Correcting for age- and sex-related variation in the total population with a linear model subsequently demonstrates that no significant correlation between heterozygosity and morphologic variation exists. No significant relationship is found in the inbred animals or subpopulations when age and sex are controlled. Previous studies have indicated that individuals proximal to the population mean for a specific polygenic trait exhibit a higher biochemical heterozygosity than individuals distant from the mean. The results presented here, which are based on more loci than many studies and a well-defined population, do not support this relationship. Substructuring of a population by age and sex can lead to spurious correlations with univariate or multivariate techniques. Comprehensive indices of genetic variation and rigorous statistical techniques should be used in future analyses. Studies that fail to recognize these design elements should be interpreted with caution.