Vitamin A Transport Mechanism of the Multitransmembrane Cell-Surface Receptor STRA6.

Vitamin A has biological functions as diverse as sensing light for vision, regulating stem cell differentiation, maintaining epithelial integrity, promoting immune competency, regulating learning and memory, and acting as a key developmental morphogen. Vitamin A derivatives have also been used in treating human diseases. If vitamin A is considered a drug that everyone needs to take to survive, evolution has come up with a natural drug delivery system that combines sustained release with precise and controlled delivery to the cells or tissues that depend on it. This "drug delivery system" is mediated by plasma retinol binding protein (RBP), the principle and specific vitamin A carrier protein in the blood, and STRA6, the cell-surface receptor for RBP that mediates cellular vitamin A uptake. The mechanism by which the RBP receptor absorbs vitamin A from the blood is distinct from other known cellular uptake mechanisms. This review summarizes recent progress in elucidating the fundamental molecular mechanism mediated by the RBP receptor and multiple newly discovered catalytic activities of this receptor, and compares this transport system with retinoid transport independent of RBP/STRA6. How to target this new type of transmembrane receptor using small molecules in treating diseases is also discussed

FAST polarization mapping of the SNR VRO 42.05.01

We have obtained the polarization data cube of the VRO 42.05.01 supernova remnant at 1240 MHz using the Five-hundred-meter Aperture Spherical radio Telescope (FAST). Three-dimensional Faraday Synthesis is applied to the FAST data to derive the Faraday depth spectrum. The peak Faraday depth map shows a large area of enhanced foreground RM of ~60 rad m-2 extending along the remnant's "wing" section, which coincides with a large-scale HI shell at -20 km/s. The two depolarization patches within the "wing" region with RM of 97 rad m-2 and 55 rad m-2 coincide with two HI structures in the HI shell. Faraday screen model fitting on the Canadian Galactic Plane Survey (CGPS) 1420 MHz full-scale polarization data reveals a distance of 0.7-0.8d_{SNR} in front of the SNR with enhanced regular magnetic field there. The highly piled-up magnetic field indicates that the HI shell at -20 km/s could originate from an old evolved SNR.Comment: 9 pages, 8 figures, accepted by Ap

Simple approach to estimating the van der Waals interaction between carbon nanotubes

The van der Waals (vdW) interactions between carbon nanotubes (CNTs) were studied based on the continuum Lennard-Jones model. It was found that all the vdW potentials between two arbitrary CNTs fall on the same curve when plotted in terms of certain reduced parameters, the well depth, and the equilibrium vdW gap. Based on this observation, an approximate approach is developed to obtain the vdW potential between two CNTs without time-consuming computations. The vdW potential estimated by this approach is close to that obtained from complex integrations. Therefore, the developed approach can greatly simplify the calculation of vdW interactions between CNTs

Melanoma-associated retinopathy

AbstractA 63-year-old Taiwanese man with a history of cutaneous melanoma presented with a rapid onset of bilateral shimmering light and blurred vision. A fundoscopic examination was normal. However, visual field examination indicated generalized depression in both eyes. Scotopic rod-specific electroretinography (ERG) was undetectable and scotopic maximal combined-cone and rod-specific ERG showed the characteristics of negative ERG (a normal a-wave and a diminished b-wave, with the b-wave smaller than the a-wave), indicating dysfunction of the bipolar cells. Melanoma-associated retinopathy (MAR) was suspected and a systemic work-up gave a diagnosis of metastatic melanoma. This case shows the typical presentation of MAR. Greater awareness of MAR in patients with unexplained visual loss may help to identify an occult focus of metastatic melanoma

Power Allocation and Time-Domain Artificial Noise Design for Wiretap OFDM with Discrete Inputs

Optimal power allocation for orthogonal frequency division multiplexing (OFDM) wiretap channels with Gaussian channel inputs has already been studied in some previous works from an information theoretical viewpoint. However, these results are not sufficient for practical system design. One reason is that discrete channel inputs, such as quadrature amplitude modulation (QAM) signals, instead of Gaussian channel inputs, are deployed in current practical wireless systems to maintain moderate peak transmission power and receiver complexity. In this paper, we investigate the power allocation and artificial noise design for OFDM wiretap channels with discrete channel inputs. We first prove that the secrecy rate function for discrete channel inputs is nonconcave with respect to the transmission power. To resolve the corresponding nonconvex secrecy rate maximization problem, we develop a low-complexity power allocation algorithm, which yields a duality gap diminishing in the order of O(1/\sqrt{N}), where N is the number of subcarriers of OFDM. We then show that independent frequency-domain artificial noise cannot improve the secrecy rate of single-antenna wiretap channels. Towards this end, we propose a novel time-domain artificial noise design which exploits temporal degrees of freedom provided by the cyclic prefix of OFDM systems {to jam the eavesdropper and boost the secrecy rate even with a single antenna at the transmitter}. Numerical results are provided to illustrate the performance of the proposed design schemes.Comment: 12 pages, 7 figures, accepted by IEEE Transactions on Wireless Communications, Jan. 201

Identification of PLXDC1 and PLXDC2 as the transmembrane receptors for the multifunctional factor PEDF.

Pigment Epithelium Derived Factor (PEDF) is a secreted factor that has broad biological activities. It was first identified as a neurotrophic factor and later as the most potent natural antiangiogenic factor, a stem cell niche factor, and an inhibitor of cancer cell growth. Numerous animal models demonstrated its therapeutic value in treating blinding diseases and diverse cancer types. A long-standing challenge is to reveal how PEDF acts on its target cells and the identities of the cell-surface receptors responsible for its activities. Here we report the identification of transmembrane proteins PLXDC1 and PLXDC2 as cell-surface receptors for PEDF. Using distinct cellular models, we demonstrate their cell type-specific receptor activities through loss of function and gain of function studies. Our experiments suggest that PEDF receptors form homooligomers under basal conditions, and PEDF dissociates the homooligomer to activate the receptors. Mutations in the intracellular domain can have profound effects on receptor activities

Thrombin Contributes to Anti-myeloperoxidase Antibody Positive IgG-Mediated Glomerular Endothelial Cells Activation Through SphK1-S1P-S1PR3 Signaling

Background: Activation of coagulation system plays an important role in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) pathogenesis. Thrombin, generated during coagulation could disrupt endothelial barrier integrity through protease-activated receptor 1 (PAR1). Our previous study found that sphingosine-1-phosphate (S1P) contributed to myeloperoxidase (MPO)-ANCA-positive IgG-induced glomerular endothelial cell (GEnC) activation through a S1P receptor (S1PR)-dependent route. In recent years, S1P signaling was reported to be involved in thrombin effects on endothelial cells. This current study investigated whether the interaction between thrombin-PAR and S1P-S1PR signaling contributed to MPO-ANCA-positive IgG-induced GEnC dysfunction.Methods: The effect of thrombin on GEnC activation was analyzed from three aspects. First, morphological alteration of GEnCs was observed. Second, permeability assay was performed to determine GEnC monolayer activation quantitatively. Third, endothelin-1 (ET-1) levels were measured. Expression levels of sphingosine kinases (SphKs) and S1PRs were detected. In addition, antagonists of PAR1 and S1PR3 were employed to determine their roles. Eventually, PAR1 and tissue factor (TF) expression levels as well as TF procoagulant activity were analyzed.Results: Thrombin induced further damage of tight junction, increase in endothelial monolayer permeability as well as upregulation of ET-1 levels in GEnCs stimulated with MPO-ANCA-positive IgG. Blocking PAR1 downregulated ET-1 levels in the supernatants of GEnCs treated by thrombin plus MPO-ANCA-positive IgG. Expression levels of SphK1, S1PR3 increased significantly in GEnCs treated with thrombin plus MPO-ANCA-positive IgG. S1P upregulated PAR1 and TF expression, and enhanced procoagulant activity of TF in MPO-ANCA-positive IgG-stimulated GEnCs.Conclusion: Thrombin synergized with SphK1-S1P-S1PR3 signaling pathway to enhance MPO-ANCA-positive IgG-mediated GEnC activation