Regulation of pregnancy-associated plasma protein A2 (PAPPA2) in a human placental trophoblast cell line (BeWo)

<p>Abstract</p> <p>Background</p> <p>Pregnancy-associated plasma protein A2 (PAPPA2) is an insulin-like growth factor-binding protein (IGFBP) protease expressed at high levels in the placenta and upregulated in pregnancies complicated by preeclampsia and HELLP (Hemolytic anemia, Elevated Liver enzymes, and Low Platelet count) syndrome. However, it is unclear whether elevated PAPPA2 expression causes abnormal placental development, or whether upregulation compensates for placental pathology. In the present study, we investigate whether PAPPA2 expression is affected by hypoxia, oxidative stress, syncytialization factors or substances known to affect the expression of PAPPA2's paralogue, PAPPA.</p> <p>Methods</p> <p>BeWo cells, a model of placental trophoblasts, were treated with one of the following: hypoxia (2% O2), oxidative stress (20 microM hydrogen peroxide), forskolin (10 microM and 100 microM), TGF-beta (10 and 50 ng/mL), TNF-alpha (100 ng/mL), IL-1beta (100 ng/mL) or PGE2 (1 microM). We used quantitative RT-PCR (qRT-PCR) to quantify the mRNA levels of PAPPA2, as well as those of PAPPA and ADAM12 since these proteases have similar substrates and are also highly expressed in the placenta. Where we observed significant effects on PAPPA2 mRNA levels, we tested for effects at the protein level using an in-cell Western assay.</p> <p>Results</p> <p>Hypoxia, but not oxidative stress, caused a 47-fold increase in PAPPA2 mRNA expression, while TNF-alpha resulted in a 6-fold increase, and both of these effects were confirmed at the protein level. PGE2 resulted in a 14-fold upregulation of PAPPA2 mRNA but this was not reflected at the protein level. Forskolin, TGF-beta and IL-1beta had no significant effect on PAPPA2 mRNA expression. We observed no effects of any treatment on PAPPA or ADAM12 expression.</p> <p>Conclusion</p> <p>Our study demonstrates that factors previously known to be highly expressed in preeclamptic placentae (PGE2 and TNF-alpha), contribute to the upregulation of PAPPA2. Hypoxia, known to occur in preeclamptic placentae, also increased PAPPA2 expression. These results are consistent with the hypothesis that PAPPA2 is upregulated as a consequence of placental pathology, rather than elevated PAPPA2 levels being a cause of preeclampsia.</p

Ground vehicle path planning on Uneven terrain Using UAV Measurement point clouds

The objective of this study is to develop a system to support rapid ground vehicle activities by planning safe travel routes for ground vehicles from point clouds of wide-area uneven terrain environments measured using UAVs. However, fast path planning is difficult in complex environments such as large, uneven terrain environments. Therefore, this paper proposes a new RRT method based on the RRT algorithm that can perform fast path planning, even in complex environments. In the proposed method, narrow areas that are difficult to be explored by ordinary RRTs are first identified in advance, and nodes are placed in these areas to guide the search. When searching with RRTs, the tree is extended via these guide nodes to efficiently traverse the narrow area. In the validation of the proposed method, a comparison was made with RRT and RRT-Connect in two environments, including narrow areas. The results show that the proposed method has a higher route discovery capability, at least two times fewer search nodes and five times faster path planning capability than other RRTs

Autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins FRLα and mDia1

Diaphanous-related formins (DRFs) are key regulators of actin cytoskeletal dynamics whose in vitro actin assembly activities are thought to be regulated by autoinhibition. However, the in vivo consequences of autoinhibition and the involvement of DRFs in specific biological processes are not well understood. In this study, we show that in the DRFs FRLα (formin-related gene in leukocytes α) and mouse diaphanous 1, autoinhibition regulates a novel membrane localization activity in vivo as well as actin assembly activity in vitro. In FRLα, the Rho family guanosine triphosphatase Cdc42 relieves the autoinhibition of both membrane localization and biochemical actin assembly activities. FRLα is required for efficient Fc-γ receptor–mediated phagocytosis and is recruited to the phagocytic cup by Cdc42. These results suggest that mutual autoinhibition of biochemical activity and cellular localization may be a general regulatory principle for DRFs and demonstrate a novel role for formins in immune function

Extraction of block walls from point clouds measured by Mobile Mapping System

To solve the problem of collapsing block walls widely used in Japan, this study proposes a method for extracting block walls using 3D point cloud data measured by the Mobile Mapping System (MMS). Unlike conventional methods, this method identifies block walls based on geometric features without relying on MMS trajectory data or deep learning inference results. In addition, the computational load is low and manual correction can be minimized. In our experiments, we used point cloud data collected in urban areas in Japan and achieved a precision of 0.750, recall of 0.810, and F-measure of 0.779. The results demonstrate the effectiveness of this method for automatic extraction of block walls and rapid assessment of collapse risk and are expected to contribute to safety measures in areas with high seismic risk

A New Possibility of Dynamical Study on Solid State Ionic Materials by Inelastic Neutron Scattering

A new technique of inelastic neutron scattering measurement utilizing the multiple incident energies is applied to the dynamical study of vitreous silica. A wide variety of extracted information from a series of two-dimensional maps of dynamical structure factor with multiple different incident energies are greatly valuable. The applicability and its expected contribution of new experimental technique into the further progress of scientific activities in solid state ionic materials are discussed.Received: 30 September 2010; Revised: 25 October 2010; Accepted: 26 October 201

A novel mechanism of actin filament processive capping by formin: solution of the rotation paradox

The FH2 domains of formin family proteins act as processive cappers of actin filaments. Previously suggested stair-stepping mechanisms of processive capping imply that a formin cap rotates persistently in one direction with respect to the filament. This challenges the formin-mediated mechanism of intracellular cable formation. We suggest a novel scenario of processive capping that is driven by developing and relaxing torsion elastic stresses. Based on the recently discovered crystal structure of an FH2–actin complex, we propose a second mode of processive capping—the screw mode. Within the screw mode, the formin dimer rotates with respect to the actin filament in the direction opposite to that generated by the stair-stepping mode so that a combination of the two modes prevents persistent torsion strain accumulation. We determine an optimal regime of processive capping, whose essence is a periodic switch between the stair-stepping and screw modes. In this regime, elastic energy does not exceed feasible values, and supercoiling of actin filaments is prevented