Cerebroplacental and Uterine Doppler Indices in Pregnancies Complicated by Congenital Heart Disease of the Fetus.

PURPOSE: Children with congenital heart disease (CHD) are known to have impaired neurodevelopment possibly influenced by altered cerebroplacental hemodynamics antenatally. We compared fetomaternal Doppler patterns in different CHD groups with published normative values during gestation. MATERIALS AND METHODS: Retrospective cohort study consisting of 248 CHD fetuses. Subgroups were generated according to the expected ascending aorta oxygen saturation: low portion of high oxygenated umbilical venous (UV) blood (group 1: n = 108), intermediate portion of UV blood due to intracardiac mixing with oxygen poor systemic blood (group 2: n = 103), high (group 3: n = 13) and low portion of UV blood without mixing of blood (group 4: n = 24). Doppler examination included umbilical artery and middle cerebral artery pulsatility index (UA-PI, MCA-PI), cerebroplacental ratio (CPR) and mean uterine artery (mUtA) PI. For mean comparisons at different gestational ages (GA), estimated marginal means from regression models are reported for GA 22 weeks (wks), GA 30 wks and GA 38 wks. RESULTS: Z-score transformed values of MCA-PI (zMCA-PI) were significantly lower in group 1 compared to all other subgroups at GA 30 wks (p < 0.05). At 38 wks, group 1 had significantly lower values of zMCA-PI and zCPR compared to groups 2 and 4. Group 1 fetuses showed a significant association between zMCA-PI and zCPR (negative) and GA as well as zmUtA-PI (positive) and GA compared to reference values. CONCLUSION: Our data confirm that CHD fetuses have a higher rate of cerebral redistribution in the third trimester. Changes in Doppler patterns were mainly observed in CHD with a low portion of UV blood in the ascending aorta.

Head Biometry in Fetuses with Isolated Congenital Heart Disease.

PURPOSE: Altered cerebral hemodynamics are involved in changes in head biometry in fetuses with congenital heart disease (CHD). We compared head growth in different CHD groups with published normative values and investigated whether CHD groups differ from each other in terms of head circumference (HC) development over gestational age (GA). MATERIALS AND METHODS: Retrospective cohort study consisting of 248 CHD fetuses. Subgroups were generated according to the expected ascending aorta oxygen saturation: Low placental blood content (BC) and therefore low oxygen delivery to the brain (group 1: n = 108), intermediate placental and systemic BC due to intracardiac mixing of blood (group 2: n = 103), high placental BC (group 3: n = 13) and low placental BC and low oxygen delivery to the brain without mixing of blood (group 4: n = 24). Furthermore, group 1 was divided into antegrade (n = 34) and retrograde (n = 74) flow through the aortic arch. Comparisons were made at a GA of 22, 30 and 38 weeks. RESULTS: Estimated values of zHC (z-score transformed) were not significantly different between the four CHD groups at the three time points in gestation (all p > 0.05). Within group 1 fetuses with retrograde aortic arch flow showed a significant negative association between HC and GA compared to reference values (b = -0.054, p < 0.001) and had significantly lower zHC values at 38 weeks (-0.836) compared to fetuses with antegrade flow (0.366, p = 0.009). CONCLUSION: Our data do not confirm that CHD fetuses in general have a significantly smaller HC. HC becomes smaller throughout gestation depending on the direction of aortic arch flow.

Adaptive evolution of genes duplicated from the Drosophila pseudoobscura neo-X chromosome.

Drosophila X chromosomes are disproportionate sources of duplicated genes, and these duplications are usually the result of retrotransposition of X-linked genes to the autosomes. The excess duplication is thought to be driven by natural selection for two reasons: X chromosomes are inactivated during spermatogenesis, and the derived copies of retroposed duplications tend to be testis expressed. Therefore, autosomal derived copies of retroposed genes provide a mechanism for their X-linked paralogs to "escape" X inactivation. Once these duplications have fixed, they may then be selected for male-specific functions. Throughout the evolution of the Drosophila genus, autosomes have fused with X chromosomes along multiple lineages giving rise to neo-X chromosomes. There has also been excess duplication from the two independent neo-X chromosomes that have been examined--one that occurred prior to the common ancestor of the willistoni species group and another that occurred along the lineage leading to Drosophila pseudoobscura. To determine what role natural selection plays in the evolution of genes duplicated from the D. pseudoobscura neo-X chromosome, we analyzed DNA sequence divergence between paralogs, polymorphism within each copy, and the expression profiles of these duplicated genes. We found that the derived copies of all duplicated genes have elevated nonsynonymous polymorphism, suggesting that they are under relaxed selective constraints. The derived copies also tend to have testis- or male-biased expression profiles regardless of their chromosome of origin. Genes duplicated from the neo-X chromosome appear to be under less constraints than those duplicated from other chromosome arms. We also find more evidence for historical adaptive evolution in genes duplicated from the neo-X chromosome, suggesting that they are under a unique selection regime in which elevated nonsynonymous polymorphism provides a large reservoir of functional variants, some of which are fixed by natural selection.

The response of Per1 to light in the suprachiasmatic nucleus of the diurnal degu (Octodon degus).

Several studies suggest that the circadian systems of diurnal mammals respond differently to daytime light than those of nocturnal mammals. We hypothesized that the photosensitive "clock" gene Per1 would respond to light exposure during subjective day in the suprachiasmatic nucleus of the diurnal rodent, Octodon degus. Tissue was collected 1.5-2 h after a 30 min light pulse presented at five timepoints across the 24 h day and compared to controls maintained under conditions of constant darkness. Per1 mRNA was quantified using in situ hybridization. Results showed that the rhythmicity and photic responsiveness of Per1 in the degu resembles that of nocturnal animals.

Protein kinase C delta (PKCdelta) interacts with microtubule organizing center (MTOC)-associated proteins and participates in meiotic spindle organization.

Defects in meiotic spindle structure can lead to chromosome segregation errors and genomic instability. In this study the potential role of protein kinase C delta (PKCdelta) on meiotic spindle organization was evaluated in mouse oocytes. PKCdelta was previously shown to be phosphorylated during meiotic maturation and concentrate on the meiotic spindle during metaphases I and II. Currently we show that when phosphorylated on Threonine 505 (pPKCdelta(Thr505)), within the activation loop of its C4 domain, PKCdelta expression was restricted to the meiotic spindle poles and a few specific cytoplasmic foci. In addition, pPKCdelta(Thr505) co-localized with two key microtubule organizing center (MTOC)-associated proteins, pericentrin and gamma-tubulin. An interaction between pPKCdelta(Thr505) and pericentrin as well as gamma-tubulin was confirmed by co-immunoprecipitation analysis using both fetal fibroblast cells and oocytes. Notably, targeted knockdown of PKCdelta expression in oocytes using short interfering RNAs effectively reduced pPKCdelta(Thr505) protein expression at MTOCs and leads to a significant (P < 0.05) disruption of meiotic spindle organization and chromosome alignment during MI and MII. Moreover, both gamma-tubulin and pericentrin expression at MTOCs were decreased in pPKCdelta(Thr505)-depleted oocytes. In sum, these results indicate that pPKCdelta(Thr505) interacts with MTOC-associated proteins and plays a role in meiotic spindle organization in mammalian oocytes.