Members of the transforming growth factor β (TGF-β) superfamily are key regulators in most developmental and physiological processes. However, the in vivo roles of TGF-β signaling in female reproduction remain uncertain. Activin receptor-like kinase 5 (ALK5) is the major type 1 receptor for the TGF-β subfamily. Absence of ALK5 leads to early embryonic lethality because of severe defects in vascular development. In this study, we conditionally ablated uterine ALK5 using progesterone receptor-cre mice to define the physiological roles of ALK5 in female reproduction. Despite normal ovarian functions and artificial decidualization in conditional knockout (cKO) mice, absence of uterine ALK5 resulted in substantially reduced female reproduction due to abnormalities observed at different stages of pregnancy, including implantation defects, disorganization of trophoblast cells, fewer uterine natural killer (uNK) cells, and impairment of spiral artery remodeling. In our microarray analysis, genes encoding proteins involved in cytokinecytokine receptor interactions and NK cell-mediated cytotoxicity were down-regulated in cKO decidua compared with control decidua. Flow cytometry confirmed a 10-fold decrease in uNK cells in cKO versus control decidua. According to these data, we hypothesize that TGF-β acts on decidual cells via ALK5 to induce expression of other growth factors and cytokines, which are key regulators in luminal epithelium proliferation, trophoblast development, and uNK maturation during pregnancy. Our findings not only generate a mouse model to study TGF-β signaling in female reproduction but also shed light on the pathogenesis of many pregnancy complications in human, such as recurrent spontaneous abortion, preeclampsia, and intrauterine growth restriction.TGF-β signaling | uterine luminal epithelium | trophoblast cells | uNK | female reproduction T he two crucial processes for the advancement of mammalian pregnancy are embryo implantation and formation of the placenta. When a blastocyst reaches the uterus, it includes two cell types, the inner cell mass, which later forms the embryo, and a layer of trophoblast, which later forms the placenta to facilitate nutrient uptake, waste elimination, and gas exchange between the embryo and the maternal uterus. In mice, the blastocyst reaches the uterus by 3.5 d postcoitum (dpc). There is only a limited time period for the uterus to support blastocyst implantation. At the beginning of the implantation widow, the closure of the uterine lumen results in closer contact between the luminal epithelium. After embryo attachment, the uterine stroma is transformed in preparation for trophoblast invasion in a process called decidualization. To achieve successful reproduction, a blastocyst competent for implantation needs to be synchronized with the proliferation and differentiation of specific uterine cell types under the control of two ovarian steroids, progesterone (P 4 ) and estradiol (E 2 ) (1, 2).Murine placentation starts from the differentiation of trophectoderm (a laye...

An automatic sleep staging method is proposed to score wakefulness and three nonrapid eye movement (NREM) stages S1, S2 and S3, based on the Empirical Mode Decomposition (EMD) algorithm. Patients with sleep disorders were tested using this method. Good agreements between manual and automatic staging results were achieved in terms of their Cohen's Kappa value.

We perform micromagnetic simulations on the switching of magnetic vortex core by using spin-polarized currents through a three-nanocontact geometry. Our simulation results show that the current combination with an appropriate current flow direction destroys the symmetry of the total effective energy of the system so that the vortex core can be easier to excite, resulting in less critical current density and a faster switching process. Besides its fundamental significance, our findings provide an additional route to incorporating magnetic vortex phenomena into data storage devices.

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