90 research outputs found

    Miscarriage and stillbirth following maternal Zika virus infection in nonhuman primates.

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    Zika virus (ZIKV) infection is associated with congenital defects and pregnancy loss. Here, we found that 26% of nonhuman primates infected with Asian/American ZIKV in early gestation experienced fetal demise later in pregnancy despite showing few clinical signs of infection. Pregnancy loss due to asymptomatic ZIKV infection may therefore be a common but under-recognized adverse outcome related to maternal ZIKV infection

    SMAD1/5 signaling in the early equine placenta regulates trophoblast differentiation and chorionic gonadotropin secretion.

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    TGFβ superfamily proteins, acting via SMAD (Sma- and Mad-related protein)2/3 pathways, regulate placental function; however, the role of SMAD1/5/8 pathway in the placenta is unknown. This study investigated the functional role of bone morphogenetic protein (BMP)4 signaling through SMAD1/5 in terminal differentiation of primary chorionic gonadotropin (CG)-secreting trophoblast. Primary equine trophoblast cells or placental tissues were isolated from day 27-34 equine conceptuses. Detected by microarray, RT-PCR, and quantitative RT-PCR, equine chorionic girdle trophoblast showed increased gene expression of receptors that bind BMP4. BMP4 mRNA expression was 20- to 60-fold higher in placental tissues adjacent to the chorionic girdle compared with chorionic girdle itself, suggesting BMP4 acts primarily in a paracrine manner on the chorionic girdle. Stimulation of chorionic girdle-trophoblast cells with BMP4 resulted in a dose-dependent and developmental stage-dependent increase in total number and proportion of terminally differentiated binucleate cells. Furthermore, BMP4 treatment induced non-CG-secreting day 31 chorionic girdle trophoblast cells to secrete CG, confirming a specific functional response to BMP4 stimulation. Inhibition of SMAD2/3 signaling combined with BMP4 treatment further enhanced differentiation of trophoblast cells. Phospho-SMAD1/5, but not phospho-SMAD2, expression as determined by Western blotting was tightly regulated during chorionic girdle trophoblast differentiation in vivo, with peak expression of phospho-SMAD1/5 in vivo noted at day 31 corresponding to maximal differentiation response of trophoblast in vitro. Collectively, these experiments demonstrate the involvement of BMP4-dependent pathways in the regulation of equine trophoblast differentiation in vivo and primary trophoblast differentiation in vitro via activation of SMAD1/5 pathway, a previously unreported mechanism of TGFβ signaling in the mammalian placenta

    A framework for the practical science necessary to restore sustainable, resilient, and biodiverse ecosystems

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    Demand for restoration of resilient, self-sustaining, and biodiverse natural ecosystems as a conservation measure is increasing globally; however, restoration efforts frequently fail to meet standards appropriate for this objective. Achieving these standards requires management underpinned by input from diverse scientific disciplines including ecology, biotechnology, engineering, soil science, ecophysiology, and genetics. Despite increasing restoration research activity, a gap between the immediate needs of restoration practitioners and the outputs of restoration science often limits the effectiveness of restoration programs. Regrettably, studies often fail to identify the practical issues most critical for restoration success. We propose that part of this oversight may result from the absence of a considered statement of the necessary practical restoration science questions. Here we develop a comprehensive framework of the research required to bridge this gap and guide effective restoration. We structure questions in five themes: (1) setting targets and planning for success, (2) sourcing biological material, (3) optimizing establishment, (4) facilitating growth and survival, and (5) restoring resilience, sustainability, and landscape integration. This framework will assist restoration practitioners and scientists to identify knowledge gaps and develop strategic research focused on applied outcomes. The breadth of questions highlights the importance of cross-discipline collaboration among restoration scientists, and while the program is broad, successful restoration projects have typically invested in many or most of these themes. Achieving restoration ecology's goal of averting biodiversity losses is a vast challenge: investment in appropriate science is urgently needed for ecological restoration to fulfill its potential and meet demand as a conservation too

    Activation of NK Cells by an Endocytosed Receptor for Soluble HLA-G

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    Signaling from endosomes is emerging as a mechanism by which selected receptors provide sustained signals distinct from those generated at the plasma membrane. The activity of natural killer (NK) cells, which are important effectors of innate immunity and regulators of adaptive immunity, is controlled primarily by receptors that are at the cell surface. Here we show that cytokine secretion by resting human NK cells is induced by soluble, but not solid-phase, antibodies to the killer cell immunoglobulin-like receptor (KIR) 2DL4, a receptor for human leukocyte antigen (HLA)-G. KIR2DL4 was constitutively internalized into Rab5-positive compartments via a dynamin-dependent process. Soluble HLA-G was endocytosed into KIR2DL4–containing compartments in NK cells and in 293T cells transfected with KIR2DL4. Chemokine secretion induced by KIR2DL4 transfection into 293T cells occurred only with recombinant forms of KIR2DL4 that trafficked to endosomes. The profile of genes up-regulated by KIR2DL4 engagement on resting NK cells revealed a proinflammatory/proangiogenic response. Soluble HLA-G induced secretion of a similar set of cytokines and chemokines. This unique stimulation of resting NK cells by soluble HLA-G, which is endocytosed by KIR2DL4, implies that NK cells may provide useful functions at sites of HLA-G expression, such as promotion of vascularization in maternal decidua during early pregnancy

    Author Correction: Drivers of seedling establishment success in dryland restoration efforts

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    1 Pág. Correción errata.In the version of this Article originally published, the surname of author Tina Parkhurst was incorrectly written as Schroeder. This has now been corrected.Peer reviewe

    New Insights Into Lithospheric Structure and Melting Beneath the Colorado Plateau

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    Abstract The Colorado Plateau and its surroundings serve as an archetypal case to investigate the interaction of mantle melting processes and lithospheric structure. It has been hypothesized that widespread Cenozoic volcanism indicates the encroachment of the convective upwelling of asthenosphere toward the Plateau center. In this study, we generate a Common Conversion Point (CCP) stack of S‐to‐p (Sp) receiver functions to image the locations of lithospheric discontinuities in the southwestern United States. Our results are broadly similar to prior work, showing a strong and continuous Negative Velocity Gradient (NVG) consistent with the Lithosphere‐Asthenosphere Boundary (LAB) over much of the study area. However, with several methodological improvements, we are able to obtain more reliable NVG depth picks below the Colorado Plateau where the LAB becomes weaker, deeper, and broader. We compare the inferred topography of NVGs with the locations of volcanoes, and find that the majority of recent volcanoes are co‐located with lithosphere that is ∼80 km thick. This appears to be the critical depth at which partial melt from upwelling asthenosphere pooling at the base of (or within) the lithosphere may percolate to the surface. We compare our CCP profiles with magma equilibration conditions determined from petrologic analysis and find good agreement between the depth of NVGs and depth of magma equilibration. This analysis provides insight into the progression of magmatism and lithospheric loss toward the center of the Colorado Plateau, and demonstrates how small‐scale processes like melting influence lithosphere‐asthenosphere interactions that persist over large temporal and spatial scales

    Модель обслуживания трафика NR на базовых станциях LTE

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    The dynamic blockage of propagation paths requires advanced techniques to preserve the session continuity in future millimeter wave (mmWave) New Radio (NR) access networks. We use the tools of queuing theory to formulate the mathematical framework capturing session service dynamics of user equipment (UE) supporting multi-band operation via 3GPP standardized multiconnectivity operation, where microwave base station (e.g., LTE or sub-6 GHz NR) is used to temporarily serve a session experiencing outage at mmWave NR BSs.Динамическая блокировка путей распространения сигнала в плотном трафике автомобильных дорог требует передовых технологий для сохранения непрерывности сессии в будущих сетях доступа технологии New Radio (NR), работающих в миллиметровом диапазоне частот (mmWave). В данной работе используются инструменты теории массового обслуживания для формализации и решения математической модели обслуживания трафика NR на базовых станциях технологии, работающей в микроволновом диапазоне частот (например, LTE или NR в полосе частот ниже 6 ГГц) при наличии конкурирующего трафика LTE. Предложенная модель отражает динамику обслуживания сессий абонентских устройств поддерживающих работу как в сетях NR, так и LTE в случае потери связи с текущей базовой станцией NR
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