Antibodies to acetylcholine receptor in parous women with myasthenia: evidence for immunization by fetal antigen

The weakness in myasthenia gravis (MG) is mediated by autoantibodies against adult muscle acetylcholine receptors (AChR) at the neuromuscular junction; most of these antibodies also bind to fetal AChR, which is present in the thymus. In rare cases, babies of mothers with MG, or even of asymptomatic mothers, develop a severe developmental condition, arthrogryposis multiplex congenita, caused by antibodies that inhibit the ion channel function of the fetal AChR while not affecting the adult AChR. Here we show that these fetal AChR inhibitory antibodies are significantly more common in females sampled after pregnancy than in those who present before pregnancy, suggesting that they may be induced by the fetus. Moreover, we were able to clone high-affinity combinatorial Fab antibodies from thymic cells of two mothers with MG who had babies with arthrogryposis multiplex congenita. These Fabs were highly specific for fetal AChR and did not bind the main immunogenic region that is common to fetal and adult AChR. The Fabs show strong biases to VH3 heavy chains and to a single Vk1 light chain in one mother. Nevertheless, they each show extensive intraclonal diversification from a highly mutated consensus sequence, consistent with antigen-driven selection in successive steps. Collectively, our results suggest that, in some cases of MG, initial immunization against fetal AChR is followed by diversification and expansion of B cells in the thymus; maternal autoimmunity will result if the immune response spreads to the main immunogenic region and other epitopes common to fetal and adult AChR

Maternal pomegranate juice intake and brain structure and function in infants with intrauterine growth restriction: A randomized controlled pilot study.

Polyphenol-rich pomegranate juice has been shown to have benefit as a neuroprotectant in animal models of neonatal hypoxic-ischemia. No published studies have investigated maternal polyphenol administration as a potential neuroprotectant in at-risk newborns, such as those with intrauterine growth restriction (IUGR). This was a randomized, placebo-controlled, double-blind pilot study to investigate the impact of maternal pomegranate juice intake in pregnancies with IUGR, on newborn brain structure and function at term-equivalent age (TEA). Mothers with IUGR at 24-34 weeks\u27 gestation were recruited from Barnes-Jewish Hospital obstetrical clinic. Consented mothers were randomized to treatment (8 oz. pomegranate juice) or placebo (8 oz. polyphenol-free juice) and continued to take juice daily from enrollment until delivery (mean 20.1 and 27.1 days, respectively). Infants underwent brain MRI at TEA (36-41 weeks\u27 gestation). Brain measures were compared between groups including: brain injury score, brain metrics, brain volumes, diffusion tensor imaging and resting state functional connectivity. Statistical analyses were undertaken as modified intention-to-treat (including randomized participants who received their allocated intervention and whose infants received brain MRI) and per-protocol (including participants who strictly adhered to the protocol, based on metabolite status). Seventy-seven mothers were randomized to treatment (n = 40) or placebo (n = 37). Of these, 28 and 27 infants, respectively, underwent term-equivalent MRI. There were no group differences in brain injury, metrics or volumes. However, treatment subjects displayed reduced diffusivity within the anterior and posterior limbs of the internal capsule compared with placebo. Resting state functional connectivity demonstrated increased correlation and covariance within several networks in treatment subjects, with alterations most apparent in the visual network in per-protocol analyses. Direct effects on health were not found. In conclusion, maternal pomegranate juice intake in pregnancies with known IUGR was associated with altered white matter organization and functional connectivity in the infant brain, suggesting differences in brain structure and function following in utero pomegranate juice exposure, warranting continued investigation. Clinical trial registration. NCT00788866, registered November 11, 2008, initial participant enrollment August 21, 2012

Measurement of the Branching Fractions for D^0 → π^-e^+v_e and D^0 → + K^-e^+V_e and Determination of │V_(cd)/V_(cs)│^2

Measurements of the exclusive branching fractions B(D^0→π^-e^+ν_e) and B(D^0→K^-e^+ν_e), using data collected at the ψ(3770) with the Mark III detector at the SLAC e^+e^- storage ring SPEAR, are used to determine the ratio of the Kobayashi-Maskawa matrix elements │V_(cd)/V_(cs)│^2 =0.057_(-0.015)^(+0.038)±0.005

Search for the decay D^0→K^0e^+e^-

A search for the decay of the charmed meson D^0→K^0e^+e^- is presented, based on data collected at the ψ(3770) resonance with the Mark III detector at the SLAC storage ring SPEAR. No evidence for this process is found, resulting in an upper limit on the decay branching ratio of 1.7×10^(-3) at the 90% confidence level

Discontinuous gas exchange in insects: Is it all in their heads?

Some insects display an intermittent pattern of gas exchange while at rest, often going hours between breaths. These discontinuous gas exchange cycles (DGCs) are known to have evolved independently within five insect orders, but their possible adaptive benefit and evolutionary origin remain an enigma. Current research is primarily concerned with testing three adaptive hypotheses: that DGCs originally evolved or are currently maintained to (1) limit respiratory water loss, (2) enhance gas exchange in subterranean environments, or (3) limit oxidative damage. These adaptive explanations fail to unite a range of apparently contradictory observations regarding the insects that display DGCs and the conditions under which they occur. Here we argue that DGCs are explained by circadian, developmental, or artificially induced reductions in brain activity. We conclude that this pattern results from the thoracic and abdominal ganglia regulating ventilation in the absence of control from higher neural centers, and it is indicative of a sleeplike state. © 2010 by The University of Chicago