Advanced maternal age causes adverse programming of mouse blastocysts leading to altered growth and impaired cardiometabolic health in post-natal life

Study question: does advanced maternal age (AMA) in mice affect cardiometabolic health during post-natal life in offspring derived from an assisted reproduction technology (ART) procedure?Summary answer: offspring derived from blastocysts collected from aged female mice displayed impaired body weight gain, blood pressure, glucose metabolism and organ allometry during post-natal life compared with offspring derived from blastocysts from young females; since all blastocysts were transferred to normalized young mothers, this effect is independent of maternal pregnancy conditions.What is known already: although studies in mice have shown that AMA can affect body weight and behaviour of offspring derived from natural reproduction, data on the effects of AMA on offspring cardiometabolic health during post-natal development are not available. Given the increasing use of ART to alleviate infertility in women of AMA, it is pivotal to develop ART–AMA models addressing the effects of maternal aging on offspring health.Study design, size, duration: blastocysts from old (34–39 weeks) or young (8–9 weeks) C57BL/6 females mated with young CBA males (13–15 weeks) were either subjected to differential cell staining (inner cell mass and trophectoderm) or underwent embryo transfer (ET) into young MF1 surrogates (8–9 weeks) to produce young (Young-ET, 9 litters) and old (Old-ET, 10 litters) embryo-derived offspring. Offspring health monitoring was carried out for 30 weeks.Participants/materials, setting, methods: all animals were fed with standard chow. Blood pressure was measured at post-natal Weeks 9, 15 and 21, and at post-natal Week 30 a glucose tolerance test (GTT) was performed. Two days after the GTT mice were killed for organ allometry. Blastocyst cell allocation variables were evaluated by T-test and developmental data were analysed with a multilevel random effects regression model.Main results and the role of chance: the total number of cells in blastocysts from aged mice was decreased (P < 0.05) relative to young mice due to a lower number of cells in the trophectoderm (mean ± SEM: 34.5 ± 2.1 versus 29.6 ± 1.0). Weekly body weight did not differ in male offspring, but an increase in body weight from Week 13 onwards was observed in Old-ET females (final body weight at post-natal Week 30: 38.5 ± 0.8 versus 33.4 ± 0.8 g, P < 0.05). Blood pressure was increased in Old-ET offspring at Weeks 9–15 in males (Week 9: 108.5 ± 3.13 versus 100.8 ± 1.5 mmHg, Week 15: 112.9 ± 3.2 versus 103.4 ± 2.1 mmHg) and Week 15 in females (115.9 ± 3.7 versus 102.8 ± 0.7 mmHg; all P < 0.05 versus Young-ET). The GTT results and organ allometry were not affected in male offspring. In contrast, Old-ET females displayed a greater (P < 0.05) peak glucose concentration at 30 min during the GTT (21.1 ± 0.4 versus 17.8 ± 1.16 mmol/l) and their spleen weight (88.2 ± 2.6 ± 105.1 ± 4.6 mg) and several organ:body weight ratios (g/g × 103) were decreased (P < 0.05 versus Young-ET), including the heart (3.7 ± 0.06 versus 4.4 ± 0.08), lungs (4.4 ± 0.1 versus 5.0 ± 0.1), spleen (2.4 ± 0.06 versus 3.2 ± 0.1) and liver (36.4 ± 0.6 versus 39.1 ± 0.9).Limitations, reasons for caution: results from experimental animal models cannot be extrapolated to humans. Nevertheless, they are valuable to develop conceptual models that can produce hypotheses for eventual testing in the target species (i.e. humans).Wider implications of the findings: our data show that offspring from mouse embryos from aged mothers can develop altered phenotypes during post-natal development compared with embryos from young mothers. Because all embryos were transferred into young mothers for the duration of pregnancy to normalize the maternal in vivo environment, our findings indicate that adverse programming via AMA is already established at the blastocyst stage. Whilst human embryos display increased aneuploidy compared with mouse, we believe our data have implications for women of AMA undergoing assisted reproduction, including surrogacy programmes.Study funding/competeing interest(s): this work was supported through the European Union FP7-CP-FP Epihealth programme (278418) to T.P.F. and the BBSRC (BB/F007450/1) to T.P.F. The authors have no conflicts of interest to declar

Rinderpest in game : a description of an outbreak and an attempt at limiting its spread by means of a bush fence

1. The history of rinderpest and of measures taken to check its spread in Central East Africa is briefly reviewed. 2. A description is given of a disease, believed to be rinderpest, affecting buffalo, eland and kudu in the Lake Rukwa trough. 3. Attention is drawn to some of the habits of game and the close association often existing between cattle and game in the dry season. 4. Subinoculations from affected buffalo and eland into susceptible young cattle and goats show that these animals suffered from rinderpest. 5. While defensive measures for cattle, namely immunization and control of movement are eminently successful, game still remains the greatest source of danger for spreading and for maintaining rinderpest. Segregation of game on a large scale, possibly with selective destruction in certain restricted areas, is the only weapon we possess at present to counter this danger. The type of bush fencing described is an attempt at evolving a practical, effective and relatively cheap means of achieving this. 6. The need for further research into the diseases of game animals and the necessity for revision of the prevalent attitude toward the game problem in Africa is emphasized.The articles have been scanned in colour with a HP Scanjet 5590; 300dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format

Non-Abelian (p,q) Strings in the Warped Deformed Conifold

We calculate the tension of $(p,q)$-strings in the warped deformed conifold using the non-Abelian DBI action. In the large flux limit, we find exact agreement with the recent expression obtained by Firouzjahi, Leblond and Henry-Tye up to and including order $1/M^2$ terms if $q$ is also taken to be large. Furthermore using the finite $q$ prescription for the symmetrised trace operation we anticipate the most general expression for the tension valid for any $(p,q)$. We find that even in this instance, corrections to the tension scale as $1/M^2$ which is not consistent with simple Casimir scaling.Comment: 18 pages, Latex, 1 figure; Added a discussion of the case when the warp factor parameter $b\neq 1$ and typos correcte

Estimating purity in terms of correlation functions

We prove a rigorous inequality estimating the purity of a reduced density matrix of a composite quantum system in terms of cross-correlation of the same state and an arbitrary product state. Various immediate applications of our result are proposed, in particular concerning Gaussian wave-packet propagation under classically regular dynamics.Comment: 3 page

Conformal Dimensions of Two-Derivative BMN Operators

We compute the anomalous dimensions of BMN operators with two covariant derivative impurities at the planar level up to first order in the effective coupling lambda'. The result equals those for two scalar impurities as well as for mixed scalar and vector impurities given in the literature. Though the results are the same, the computation is very different from the scalar case. This is basically due to the existence of a non-vanishing overlap between the derivative impurity and the ``background'' field Z. We present details of these differences and their consequences.Comment: 27 pages, v2: references added, minor change

Evolution of entanglement under echo dynamics

Echo dynamics and fidelity are often used to discuss stability in quantum information processing and quantum chaos. Yet fidelity yields no information about entanglement, the characteristic property of quantum mechanics. We study the evolution of entanglement in echo dynamics. We find qualitatively different behavior between integrable and chaotic systems on one hand and between random and coherent initial states for integrable systems on the other. For the latter the evolution of entanglement is given by a classical time scale. Analytic results are illustrated numerically in a Jaynes Cummings model.Comment: 5 RevTeX pages, 3 EPS figures (one color) ; v2: considerable revision ;inequality proof omitte

Electrified Fuzzy Spheres and Funnels in Curved Backgrounds

We use the non-Abelian DBI action to study the dynamics of $N$ coincident $Dp$-branes in an arbitrary curved background, with the presence of a homogenous world-volume electric field. The solutions are natural extensions of those without electric fields, and imply that the spheres will collapse toward zero size. We then go on to consider the $D1-D3$ intersection in a curved background and find various dualities and automorphisms of the general equations of motion. It is possible to map the dynamical equation of motion to the static one via Wick rotation, however the additional spatial dependence of the metric prevents this mapping from being invertible. Instead we find that a double Wick rotation leaves the static equation invariant. This is very different from the behaviour in Minkowski space. We go on to construct the most general static fuzzy funnel solutions for an arbitrary metric either by solving the static equations of motion, or by finding configurations which minimise the energy. As a consistency check we construct the Abelian $D3$-brane world-volume theory in the same generic background and find solutions consistent with energy minimisation. In the $NS$5-brane background we find time dependent solutions to the equations of motion, representing a time dependent fuzzy funnel. These solutions match those obtained from the $D$-string picture to leading order suggesting that the action in the large $N$ limit does not need corrections. We conclude by generalising our solutions to higher dimensional fuzzy funnels.Comment: 38 pages, Latex; references adde

Fluctuating Fuzzy Funnels

It is well known that a D-string ending on a D3, D5 or D7 brane is described in terms of a non-commutative fuzzy funnel geometry. In this article, we give a numerical study of the fluctuations about this leading geometry. This allows us to investigate issues related to the stability and moduli space of these solutions. We comment on the comparison to the linearized fluctuations in supergravity.Comment: 24 pages, 3 figures; v2 references added and correcte

Fuzzy Sphere Dynamics and Non-Abelian DBI in Curved Backgrounds

We consider the non-Abelian action for the dynamics of $N Dp'$-branes in the background of $M Dp$-branes, which parameterises a fuzzy sphere using the SU(2) algebra. We find that the curved background leads to collapsing solutions for the fuzzy sphere except when we have $D0$ branes in the $D6$ background, which is a realisation of the gravitational Myers effect. Furthermore we find the equations of motion in the Abelian and non-Abelian theories are identical in the large $N$ limit. By picking a specific ansatz we find that we can incorporate angular momentum into the action, although this imposes restriction upon the dimensionality of the background solutions. We also consider the case of non-Abelian non-BPS branes, and examine the resultant dynamics using world-volume symmetry transformations. We find that the fuzzy sphere always collapses but the solutions are sensitive to the combination of the two conserved charges and we can find expanding solutions with turning points. We go on to consider the coincident $NS$5-brane background, and again construct the non-Abelian theory for both BPS and non-BPS branes. In the latter case we must use symmetry arguments to find additional conserved charges on the world-volumes to solve the equations of motion. We find that in the Non-BPS case there is a turning solution for specific regions of the tachyon and radion fields. Finally we investigate the more general dynamics of fuzzy $\mathbb{S}^{2k}$ in the $Dp$-brane background, and find collapsing solutions in all cases.Comment: 49 pages, 3 figures, Latex; Version to appear in JHE

Microscopic theory of atom-molecule oscillations in a Bose-Einstein condensate

In a recent experiment at JILA [E.A. Donley et al., Nature (London) 417, 529 (2002)] an initially pure condensate of Rb-85 atoms was exposed to a specially designed time dependent magnetic field pulse in the vicinity of a Feshbach resonance. The production of new components of the gas as well as their oscillatory behavior have been reported. We apply a microscopic theory of the gas to identify these components and determine their physical properties. Our time dependent studies allow us to explain the observed dynamic evolution of all fractions, and to identify the physical relevance of the pulse shape. Based on ab initio predictions, our theory strongly supports the view that the experiments have produced a molecular condensate.Comment: 18 pages, 20 figure