Although it is widely assumed that a maternal contribution to fetal serotonin (5-hydroxytryptamine or 5-HT) levels during pregnancy is important in neurodevelopment, there is little direct experimental evidence to support the idea. Bonnin et al. use new techniques to determine that during early pregnancy the placenta is a significant source of 5-HT, made from maternal tryptophan precursors in both mice and humans. Later in pregnancy, an endogenous 5-HT source in the fetus takes over. Serotonin (5-hydroxytryptamine or 5-HT) is thought to regulate neurodevelopmental processes through maternal–fetal interactions that have long-term mental health implications. It is thought that beyond fetal 5-HT neurons there are significant maternal contributions to fetal 5-HT during pregnancy1,2 but this has not been tested empirically. To examine putative central and peripheral sources of embryonic brain 5-HT, we used Pet1−/− (also called Fev) mice in which most dorsal raphe neurons lack 5-HT3. We detected previously unknown differences in accumulation of 5-HT between the forebrain and hindbrain during early and late fetal stages, through an exogenous source of 5-HT which is not of maternal origin. Using additional genetic strategies, a new technology for studying placental biology ex vivo and direct manipulation of placental neosynthesis, we investigated the nature of this exogenous source. We uncovered a placental 5-HT synthetic pathway from a maternal tryptophan precursor in both mice and humans. This study reveals a new, direct role for placental metabolic pathways in modulating fetal brain development and indicates that maternal–placental–fetal interactions could underlie the pronounced impact of 5-HT on long-lasting mental health outcomes.

Preeclampsia remains a major problem worldwide for mothers and babies. Despite intensive study, we have not been able to improve the management or early recognition of preeclampsia. At least part of this is because of failure to standardize the approach to studying this complex syndrome. It is possible that within the syndrome there may be different phenotypes with pathogenic pathways that differ between the subtypes. The capacity to recognize and to exploit different subtypes is of obvious importance for prediction, prevention, and treatment. We present a strategy for research to study preeclampsia, which will allow discrimination of such possible subtypes and also allow comparison and perhaps combinations of findings in different studies by standardized data and biosample collection. To make studies relevant to current clinical practice, the definition of preeclampsia can be that currently used and accepted. However, more importantly, sufficient data should be collected to allow other diagnostic criteria to be used and applied retrospectively. To that end, we present what we consider to be the minimum requirements for a data set in a study of preeclampsia that will facilitate comparisons. We also present a comprehensive or optimal data set for in-depth investigation of pathophysiology. As we approach the definition of phenotypes of preeclampsia by clinical and biochemical criteria, adherence to standardized protocols will hasten our understanding of the causes of preeclampsia and development of targeted treatment strategies

We present a measurement of the branching fraction and photon-energy spectrum for the decay $B\to X_s\gamma$ using data from the BABAR experiment. The data sample corresponds to an integrated luminosity of $210{\mathrm{fb}}^{-1}$, from which approximately 680 000 $B\overline{B}$ events are tagged by a fully reconstructed hadronic decay of one of the $B$ mesons. In the decay of the second $B$ meson, an isolated high-energy photon is identified. We measure $\mathcal{B}(B\to X_s\gamma )=(3.66\pm {0.85}_{\mathrm{stat}}\pm {0.60}_{\mathrm{syst}})\times {10}^{-4}$ for photon energies $E_{\gamma }$ above 1.9 GeV in the $B$ rest frame. From the measured spectrum we calculate the first and second moments for different minimum photon energies, which are used to extract the heavy-quark parameters $m_{\mathrm{b}}$ and ${\mu }_{\pi }^2$. In addition, measurements of the direct $CP$ asymmetry and isospin asymmetry are presented.

SERPINA3 (Serpin peptidase inhibitor clade A member 3), also known as a1-antichymotrypsin, is a serine protease inhibitor involved in a wide range of biological processes. Recently, it has been shown to be up-regulated in human placental diseases in association with a hypomethylation of the 5′ region of the gene. In the present study, we show that the promoter of SERPINA3 is transcriptionally activated by three transcription factors (TFs) (SP1, MZF1 and ZBTB7B), the level of induction being dependent on the rs1884082 single nucleotide polymorphism (SNP) located inside the promoter, the T allele being consistently induced to a higher level than the G, with or without added TFs. When the promoter was methylated, the response to ZBTB7B was allele specific (the G allele was strongly induced, while the T allele was strongly down-regulated). We propose an adaptive model to explain the interest of such a regulation for placental function and homeostasis. Overexpression of SERPINA3 in JEG-3 cells, a trophoblast cell model, decreased cell adhesion to the extracellular matrix and to neighboring cells, but protects them from apoptosis, suggesting a way by which this factor could be deleterious at high doses. In addition, we show in different human populations that the T allele appears to predispose to Intra Uterine Growth Restriction (IUGR), while a G allele at a second SNP located in the second exon (rs4634) increases the risk of preeclampsia. Our results provide mechanistic views inside the involvement of SERPINA3 in placental diseases, through its regulation by a combination of epigenetic, genetic and TF-mediated regulations.

We present updated measurements of the branching fractions and $CP$ asymmetries for $B^0\to {\pi }^0{\pi }^0$, $B^{\pm }\to {\pi }^{\pm }{\pi }^0$, and $B^{\pm }\to K^{\pm }{\pi }^0$. Based on a sample of $383\times {10}^6$ $\mathit{{\rm Y}}(4S)\to B\overline{B}$ decays collected by the BABAR detector at the PEP-II asymmetric-energy $B$ factory at SLAC, we measure $\mathcal{B}(B^0\to {\pi }^0{\pi }^0)=(1.47\pm 0.25\pm 0.12)\times {10}^{-6}$, $\mathcal{B}(B^{\pm }\to {\pi }^{\pm }{\pi }^0)=(5.02\pm 0.46\pm 0.29)\times {10}^{-6}$, and $\mathcal{B}(B^{\pm }\to K^{\pm }{\pi }^0)=(13.6\pm 0.6\pm 0.7)\times {10}^{-6}$. We also measure the $CP$ asymmetries ${\mathcal{C}}_{{\pi }^0{\pi }^0}=-0.49\pm 0.35\pm 0.05$, ${\mathcal{A}}_{{\pi }^{\pm }{\pi }^0}=0.03\pm 0.08\pm 0.01$, and ${\mathcal{A}}_{K^{\pm }{\pi }^0}=0.030\pm 0.039\pm 0.010$. Finally, we present bounds on the Cabibbo-Kobayashi-Maskawa angle $\alpha$ using isospin relations.

Our objective was to examine whether delivery at 37 weeks of gestation alters adverse pregnancy outcomes in Latina patients with intrahepatic cholestasis of pregnancy (ICP). We conducted a retrospective chart review of Latina patients who delivered at our institution coded with ICP between 2000 and 2007. During this time period it was our practice to offer delivery to patients with ICP at 37 weeks of gestation. Subjects were classified into three groups according to total bile acid (TBA) concentration: < 20 μmol/L (mild ICP), ≥ 20 μmol/L and < 40 μmol/L (moderate ICP), and ≥ 40 μmol/L (severe ICP). Meconium passage was observed in no births in patients with mild IC, but was found in 18% of deliveries with moderate/severe ICP. The risk of meconium passage increased linearly, with a 19.7% increased risk for each 10 μmol/L increase in TBA concentration (p = 0.001). There was no association with higher TBA concentration and other adverse outcomes. There was no difference in adverse outcomes between moderate and severe ICP. We concluded that in our Latina population with ICP, an association existed between meconium passage and moderate/severe ICP. Delivering at 37 weeks was associated with a low risk of adverse outcomes due to ICP among all patients, including those with higher TBA concentrations.