Birthweight discordance in multiple pregnancy.

This paper reviews several aspects of discordant growth in multiple pregnancies. Discordant growth is not a chance event and therefore several patterns can be discerned. About 75% of twins exhibit < 15% discordance (concordant), 20% are 15-25% (mildly) discordant, and about 5% are more than 25% (severely) discordant. Higher frequencies and increased severity are seen among triplets. Five observations regarding discordance became generally accepted: (a) not all discordant pairs are similar; (b) the larger the discordance level the greater is the risk for an adverse outcome; (c) discordant growth does not necessarily represent growth restriction; (d) a discordance level may have a different clinical implication in different gestational ages; and (e) the smaller fetuses in severely discordant pairs are at disproportionate risk for neonatal mortality. Mild discordance may represent a normal variation between sibs whereas severely discordant pairs often exhibit patterns of growth restriction. Not infrequently, discordance may represent an adaptation to the limited intrauterine space in order to increase gestational age.     

In vitro development of embryos from Sinclair miniature pigs: a preliminary report

The goal of this project was to identify conditions that result in development from the zygote or the 2-cell stage Sinclair miniature pig embryos to the blastocyst stage. Four media were selected, 2 that have been shown to result in in vitro development in domestic pigs (Hepes buffered Tyrode's medium and Whitten's medium), 1 that is compatible with similar development in the cow (CR-1), and 1 that is compatible with development in the mouse (CZB). One- and two-cell stage embryos from Sinclair miniature pigs were flushed from oviducts in Hepes buffered Tyrode's medium, allocated to 1 of the 4 media and cultured for 120 h. At the end of the culture period, embryos were morphologically scored and nuclei were counted. Morphology scores were lowest for Hepes buffered Tyrode's medium but were not different for Whitten's medium, CZB or CR-1. The highest (P < 0.07) number of nuclei was present in the oocytes cultured in Whitten's medium (21.3), with CR-1 (15.7) and CZB (16.5) not differing significantly. Similar to the morphology scores, Hepes buffered Tyrode's medium resulted in the lowest number nuclei (5.5). In a parallel experiment, domestic pig embryos were cultured in Hepes buffered Tyrode's medium versus Whitten's medium. The domestic pig embryos, while also developing better in Whitten's Medium, developed better in the Hepes buffered Tyrode's medium than did the embryos from Sinclair pigs. Thus, the Sinclair pig embryo develops best if placed in Whitten's Medium.     

Nonlinear sequence-dependent structure of nigral dopamine neuron interspike interval firing patterns.

Firing patterns of 15 dopamine neurons in the rat substantia nigra were studied. These cells alternated between two firing modes, single-spike and bursting, which interwove to produce irregular, aperiodic interspike interval (ISI) patterns. When examined by linear autocorrelation analysis, these patterns appeared to reflect a primarily stochastic or random process. However, dynamical analysis revealed that the sequential behavior of a majority of these cells expressed "higher-dimensional" nonlinear deterministic structure. Dimensionality refers to the number of degrees of freedom or complexity of a time series. Bursting was statistically associated with some aspects of nonlinear ISI sequence dependence. Controlling for the effects of nonstationarity substantially increased overall predictability of ISI sequences. We hypothesize that the nonlinear deterministic structure of ISI firing patterns reflects the neuron's response to coordinated synaptic inputs emerging from neural circuit interactions.     

Hyperbolic Modeling of Starburst Dendrimers

Starburst dendrimers are highly branched oligomers. A rigid dendritic hydrocarbon, C₁₁₃₄H₁₁₄₆, has recently been synthesized. It consists of 94 phenylacetylene units displayed in a self-similar two-dimensional skeleton isomorphous to the three-coordinated Bethe lattice. The three-dimensional representation of phenylacetylene dendrimer shows a globular architecture with large voids and niches in its interior, characteristic of hyperbolic surfaces. This work investigates the geometrical scaling behavior of this starburst dendrimer using the symmetry properties of a Bethe lattice embedded in the hyperbolic plane. The results for C₁₁₃₄H₁₁₄₆ provide its density profile and an upper bound for its macromolecular size. This revised version was published online in June 2006 with corrections to the Cover Date.     

Analysis of physiological and molecular changes in melon (Cucumis melo L.) varieties with different rates of ripening

Seven melon varieties (Alpha, Delada, Marygold, Sirio, Topper,Tornado, and Viva) known to exhibit differences in their ripeningbehaviour were used in this study. The expression of mRNAs forACC oxidase (MEL1) and phytoene synthase (MEL5), required forsynthesis of ethylene and carotenoids, respectively, and tworipening-related cDNAs (MEL2 and MEL7), of unknown function,was examined and correlated with the development of colour andsoftening of fruits. The MEL2 and MEL7 mRNAs were present andaccumulated in all varieties, indicating their importance inmelon fruit ripening. The fruits of Delada and Marygold didnot show any change in the colour of the flesh even at 50 daa(days after anthesis). All other varieties changed colour fromgreen to orange between 25–30 daa. The phytoene synthasemRNA levels in most varieties seemed to be unrelated to changein fruit flesh colour. The firmness of all the fruits was reducedsignificantly between 25 and 40 daa. The expression of ACC oxidasemRNA showed the most variation among the different varitiesand was delayed in Sirio and undetectable in Marygold fruitseven at 40 daa. Varieties with delayed expression of ACC oxidasemRNAs after anthesis also showed delayed softening during ripening.The prospects of genetic engineering and breeding for melonfruits with improved quality characteristics and extended storagelife are discussed. Key words: Cucumis melo, colour development, melon varieties, ripening genes, softening     

Ethanol Promotes Apoptosis in Cerebellar Granule Cells by Inhibiting the Trophic Effect of NMDA

Abstract: When primary cultures of cerebellar granule neurons are grown in a physiological concentration of KCl (5 m M ) they undergo apoptosis, which can be prevented by growing the cells in the presence of N -methyl- d -aspartate (NMDA). We now show that ethanol inhibits this trophic effect of NMDA, i.e., promotes apoptosis, and also inhibits the NMDA-induced increase in intracellular Ca²⁺ concentration in cells grown in 5 m M KCl. Both effects of ethanol show a similar concentration dependence and are reversed by a high concentration of glycine, the co-agonist at the NMDA receptor. The data suggest that the effect of ethanol on apoptosis is mediated, at least in part, by inhibition of NMDA receptor function. This effect of ethanol to increase apoptosis could contribute to the previously described in vivo sensitivity of the developing cerebellum to ethanol-induced damage.     

Capillary endothelial cell tropism of PVC-211 murine leukemia virus and its application for gene transduction.

PVC-211 murine leukemia virus (MuLV) causes neurodegenerative disease following inoculation of neonatal, but not adult, mice and rats. It was previously shown that tropism for brain capillary endothelial cells (CEC) was a determinant of the viral neuropathogenicity. In this study, we demonstrate that host age-dependent replication of PVC-211 MuLV in vivo occurs in CEC in the brain as well as in other organs, such as the liver, kidney, and heart. In contrast, primary explant cultures of CEC derived from brains and livers of adult and neonatal rats could be infected by PVC-211 MuLV, suggesting that the age-dependent susceptibility was abrogated in vitro. Although CEC were generally less susceptible to MuLV-mediated gene transduction than fibroblasts, treatment of CEC with 2-deoxyglucose followed by inoculation of a PVC-211 MuLV-pseudotyped vector in the absence of heparin improved the transduction efficiency. These observations support the possibility that PVC-211 MuLV may be useful for establishing models of CEC gene transduction.     

A Genetic Polymorphism in Coumarin 7-Hydroxylation: Sequence of the Human CYP2A Gnes and Identification of Variant CYP2A6 Alleles

A group of human cytochrome P450 genes encompassing the CYP2A, CYP2B, and CYP2F subfamilies were cloned and assembled into a 350-kb contig localized on the long arm of chromosome 19. Three complete CYP2A genes—CYP2A6, CYP2A7, and CYP2A13—plus two pseudogenes truncated after exon 5, were identified and sequenced. A variant CYP2A6 allele that differed from the corresponding CYP2A6 and CYP2A7 cDNAs previously sequenced was found and was designated CYP2A6ν2. Sequence differences in the CYP2A6ν2 gene are restricted to regions encompassing exons 3, 6, and 8, which bear sequence relatedness with the corresponding exons of the CYP2A7 gene, located downstream and centromeric of CYP2A6ν2, suggesting recent gene-conversion events. The sequencing of all the CYP2A genes allowed the design of a PCR diagnostic test for the normal CYP2A6 allele, the CYP2A6ν2 allele, and a variant—designated CYP2A6ν1—that encodes an enzyme with a single inactivating amino acid change. These variant alleles were found in individuals who were deficient in their ability to metabolize the CYP2A6 probe drug coumarin. The allelic frequencies of CYP2A6ν1 and CYP2A6ν2 differed significantly between Caucasian, Asian, and African-American populations. These studies establish the existence of a new cytochrome P450 genetic polymorphism.     

Morphometric analysis of atrial natriuretic peptide-containing granules in atriocytes of rats with experimental congestive heart failure

The morphometric characteristics of atrial natriuretic peptide-containing granules were studied in atrial myoendocrine cells of rats with aorto-caval fistula, an experimental model of congestive heart failure. A total of 6680 granules of control and aorto-caval rats were analyzed by a computerized image analysis system that evaluated the number and sectioned surface area of granules and their subcellular location. Compared with control animals, rats with congestive heart failure displayed a slight increase in the number of peripheral granules, adjacent to the sarcolemma, but not centrally located in the Golgi areas. The mean sectioned surface area of granules in rats with congestive heart failure was about 50% of that in controls, both in the right and left atria. Rats with aortocaval fistula had a higher percent of small granules and lower percent of large granules compared with controls. The data demonstrate different morphometric characteristics in atrial natriuretic peptide-containing granules in atriocytes in rats with experimental congestive heart failure; this may reflect the enhanced synthesis and release of atrial natriuretic peptide in heart failure.