Genetic Normalization of Differentiating Aneuploid Human Embryos

Early embryogenesis involves a series of dynamic processes, many of which are currently not well described or understood. Aneuploidy and aneuploid mosaicism, a mixture of aneuploid and euploid cells within one embryo, in early embryonic development are principal causes of developmental failure.^1,2^ Here we show that human embryos demonstrate a significant rate of genetic correction of aneuploidy, or "genetic normalization" when cultured from the cleavage stage on day 3 (Cleavage) to the blastocyst stage on day 5 (Blastocyst) using routine in vitro fertilization (IVF) laboratory conditions. One hundred and twenty-six human Cleavage stage embryos were evaluated for clinically indicated preimplantation genetic screening (PGS). Sixty-four of these embryos were found to be aneuploid following Cleavage stage embryo biopsy and single nucleotide polymorphism (SNP) 23 chromosome molecular karyotype (microarray). Of these, 25 survived to the Blastocyst stage of development and repeat microarray evaluation was performed. The inner cell mass (ICM), containing cells destined to form the fetus, and the trophectoderm (TE), containing cells destined to form the placenta were evaluated. Sixteen of 25 embryos (64%) [95% CI: 44-80%] possessed diploid karyotypes in both the ICM and TE cell populations. An additional three Blastocyst stage embryos showed genetic correction of the TE but not the ICM and one Blastocyst stage embryo showed the reverse. Mosaicism (exceeding 5%), was not detected in any of the ICM and TE samples analyzed. Recognizing that genetic normalization may occur in developing human embryos has important implications for stem cell biology, preimplantation and developmental genetics, embryology, and reproductive medicine. 

1)Hassold, T. et al. A cytogenetic study of 1000 spontaneous abortions. Ann Hum Genet. 44, 151-78 (1980).
2)Menasha, J., Levy, B., Hirschhorn, K., & Kardon, N.B. Incidence and spectrum of chromosome abnormalities in spontaneous abortions: new insights from a 12-year study. Genet Med. 7, 251-63 (2005)

A Combined Preconditioning Strategy for Nonsymmetric Systems

We present and analyze a class of nonsymmetric preconditioners within a normal (weighted least-squares) matrix form for use in GMRES to solve nonsymmetric matrix problems that typically arise in finite element discretizations. An example of the additive Schwarz method applied to nonsymmetric but definite matrices is presented for which the abstract assumptions are verified. A variable preconditioner, combining the original nonsymmetric one and a weighted least-squares version of it, is shown to be convergent and provides a viable strategy for using nonsymmetric preconditioners in practice. Numerical results are included to assess the theory and the performance of the proposed preconditioners.Comment: 26 pages, 3 figure

A graph-theoretic condition for irreducibility of a set of cone preserving matrices

Given a closed, convex and pointed cone K in R^n , we present a result which infers K-irreducibility of sets of K-quasipositive matrices from strong connectedness of certain bipartite digraphs. The matrix-sets are defined via products, and the main result is relevant to applications in biology and chemistry. Several examples are presented

Hydrological summary for the United Kingdom: June 2014

The monthly summary of hydrological conditions in the United Kingdom is compiled as part of the National Hydrological Monitoring Programme (a joint CEH and BGS enterprise). The report features contemporary data for rainfall, river flow, reservoir and groundwater levels in the form of maps and graphs. A commentary is provided on the status of the nation’s water resources and any notable hydrological events during the month. The National River Flow and National Groundwater Level Archives help provide an historical context for these contemporary assessments. Financial support for the production of the Hydrological Summaries is provided by Defra, the Environment Agency, the Scottish Environment Protection Agency, the Rivers Agency in Northern Ireland and the Office of Water Services

2018 International Consensus Statement on Golf and Health to guide action by people, policymakers and the golf industry

Scientific and public interest relating to golf and health has increased recently. Players, potential players, the golf industry and facilities, and decision makers will benefit from a better understanding of how to realise potential health benefits and minimise health issues related to golf. We outline an International Consensus on Golf and Health. A systematic literature review informed the development of a survey. Utilising modified Delphi methods, an expert panel of 25 persons including public health and golf industry leaders, took part in serial surveys providing feedback on suggested items, and proposing new items. Predefined criteria for agreement determined whether each item was included within each survey round and in the final consensus. The working group identified 79 scientifically supportable statement items from literature review and discussions. Twenty-five experts (100%) completed all three rounds of surveys, rating each item, and suggesting modifications and/ or new items for inclusion in subsequent surveys. After three rounds, 83 items achieved consensus with each with &gt;75% agreement and &lt;10% disagreement. These items are included in the final International Consensus on Golf and Health. The final consensus presented here can inform scientific knowledge, and action plans for (1) golfers and potential golfers, (2) golf facilities and the golf industry, and (3) policy and decision makers external to golf. These outputs, if widely adopted, will contribute to an improved understanding of golf and health, and aid these groups in making evidence-informed decisions to improve health and well-being.</p

CD155 on HIV-infected cells is not modulated by HIV-1 Vpu and Nef but synergizes with NKG2D ligands to trigger NK cell lysis of autologous primary HIV-infected cells

Activation of primary CD4(+) T cells induces the CD155, but not the CD112 ligands for the natural killer (NK) cell activation receptor (aNKR) CD226 [DNAX accessory molecule-1 (DNAM-1)]. We hypothesize that HIV productively infects activated CD4(+) T cells and makes itself vulnerable to NK cell-mediated lysis when CD155 on infected T cells engages DNAM-1. The primary objective of this study is to determine whether CD155 alone or together with NKG2D ligands triggers autologous NK cell lysis of HIV-infected T cells and whether HIV modulates CD155. To determine whether HIV modulates this activation ligand, we infected “activated” CD4(+) T cells with HIV in the absence or presence of Nef and/or Vpu and determined by flow cytometry whether they modulated CD155. To determine if CD155 alone, or together with NKG2D ligands, triggered NK cell lysis of autologous HIV-infected T cells, we treated purified NK cells with DNAM-1 and/or NKG2D blocking antibodies before the addition of purified autologous HIV-infected cells in cytolytic assays. Finally, we determined whether DNAM-1 works together with NKG2D as an NK cell coactivation receptor (caNKR) or whether they work independently as aNKRs to induce an NK cell lytic response. We demonstrate that HIV and specifically Nef and/or Vpu do not modulate CD155 on infected primary T cells; and both CD155 and NKG2D ligands synergize as aNKRs to trigger NK cell lysis of the infected cell