Androgen receptor acetylation governs trans activation and MEKK1-induced apoptosis without affecting in vitro sumoylation and trans-repression function

This work was supported by grants from the NIH (R01CA86072 to R.G.P. and R01CA72038-01 to S.A.W.F.) and The Susan Komen Breast Cancer Foundation (to R.G.P.). R.T.H. and E.J. were supported by the Medical Research Council. Y.-G.Y. is supported by grant CA26504 to E. R. Stanley. Work conducted at the Albert Einstein College of Medicine was supported by Cancer Center Core National Institutes of Health grant 5-P30-CA13330-26.The androgen receptor (AR) is a nuclear hormone receptor superfamily member that conveys both traits repression and ligand-dependent trans-activation function. Activation of the AR by dihydrotestosterone (DHT) regulates diverse physiological functions including secondary sexual differentiation in the male and the induction of apoptosis by the JNK kinase, MEKK1. The AR is posttranslationally modified on lysine residues by acetylation and sumoylation. The histone acetylases p300 and P/CAF directly acetylate the AR in vitro at a conserved KLKK motif. To determine the functional properties governed by AR acetylation, point mutations of the KLKK motif that abrogated acetylation were engineered and examined in vitro and in vivo. The AR acetylation site point mutants showed wild-type trans repression of NF-kappaS, AP-1, and Sp1 activity; wild-type sumoylation in vitro; wild-type ligand binding; and ligand-induced conformational changes. However, acetylation-deficient AR mutants were selectively defective in DHT-induced trans activation of androgen-responsive reporter genes and coactivation by SRC1, Ubc9, TIP60, and p300. The AR acetylation site mutant showed 10-fold increased binding of the N-CoR corepressor compared with the AR wild type in the presence of ligand. Furthermore, histone deacetylase 1 (HDAC1) bound the AR both in vivo and in cultured cells and HDAC1 binding to the AR was disengaged in a DHT-dependent manner. MEKK1 induced AR-dependent apoptosis in prostate cancer cells. The AR acetylation mutant was defective in MEKK1-induced apoptosis, suggesting that the conserved AR acetylation site contributes to a pathway governing prostate cancer cellular survival. As AR lysine residue mutations that abrogate acetylation correlate with enhanced binding of the N-CoR repressor in cultured cells, the conserved AR motif may directly or indirectly regulate ligand-dependent corepressor disengagement and, thereby, ligand-dependent trans activation.Publisher PDFPeer reviewe

The intrinsic disorder related alloy scattering in ZrNiSn half-Heusler thermoelectric materials

The intrinsic structural disorder dramatically affects the thermal and electronic transport in semiconductors. Although normally considered an ordered compound, the half-Heusler ZrNiSn displays many transport characteristics of a disordered alloy. Similar to the (Zr,Hf)NiSn based solid solutions, the unsubstituted ZrNiSn compound also exhibits charge transport dominated by alloy scattering, as demonstrated in this work. The unexpected charge transport, even in ZrNiSn which is normally considered fully ordered, can be explained by the Ni partially filling interstitial sites in this half-Heusler system. The influence of the disordering and defects in crystal structure on the electron transport process has also been quantitatively analyzed in ZrNiSn1-xSbx with carrier concentration n_H ranging from 5.0×10^(19) to 2.3×10^(21) cm^(−3) by changing Sb dopant content. The optimized carrier concentration n_H ≈ 3–4×10^(20) cm^(−2) results in ZT ≈ 0.8 at 875K. This work suggests that MNiSn (M = Hf, Zr, Ti) and perhaps most other half-Heusler thermoelectric materials should be considered highly disordered especially when trying to understand the electronic and phonon structure and transport features

Robot manipulator self-identification for surrounding obstacle detection

Obstacle detection plays an important role for robot collision avoidance and motion planning. This paper focuses on the study of the collision prediction of a dual-arm robot based on a 3D point cloud. Firstly, a self-identification method is presented based on the over-segmentation approach and the forward kinematic model of the robot. Secondly, a simplified 3D model of the robot is generated using the segmented point cloud. Finally, a collision prediction algorithm is proposed to estimate the collision parameters in real-time. Experimental studies using the KinectⓇ sensor and the BaxterⓇ robot have been performed to demonstrate the performance of the proposed algorithm

Anisotropic electrical and thermal magnetotransport in the magnetic semimetal GdPtBi

The half-Heusler rare-earth intermetallic GdPtBi has recently gained attention due to peculiar magnetotransport phenomena that have been associated with the possible existence of Weyl fermions, thought to arise from the crossings of spin-split conduction and valence bands. On the other hand, similar magnetotransport phenomena observed in other rare-earth intermetallics have often been attributed to the interaction of itinerant carriers with localized magnetic moments stemming from the $4f$-shell of the rare-earth element. In order to address the origin of the magnetotransport phenomena in GdPtBi, we performed a comprehensive study of the magnetization, electrical and thermal magnetoresistivity on two single-crystalline GdPtBi samples. In addition, we performed an analysis of the Fermi surface via Shubnikov-de Haas oscillations in one of the samples and compared the results to \emph{ab initio} band structure calculations. Our findings indicate that the electrical and thermal magnetotransport in GdPtBi cannot be solely explained by Weyl physics and is strongly influenced by the interaction of both itinerant charge carriers and phonons with localized magnetic Gd-ions and possibly also paramagnetic impurities.Comment: 11 figure

High density lipoprotein promotes proliferation of adipose-derived stem cells via S1P1 receptor and Akt, ERK1/2 signal pathways

Introduction: Adipose-derived stem cells (ADSC) are non-hematopoietic mesenchymal stem cells that have shown great promise in their ability to differentiate into multiple cell lineages. Their ubiquitous nature and the ease of harvesting have attracted the attention of many researchers, and they pose as an ideal candidate for applications in regenerative medicine. Several reports have demonstrated that transplanting ADSC can promote repair of injured tissue and angiogenesis in animal models. Survival of these cells after transplant remains a key limiting factor for the success of ADSC transplantation. Circulating factors like High Density Lipoprotein (HDL) has been known to promote survival of other stems cells like bone marrow derived stem cells and endothelial progenitor cells, both by proliferation and by inhibiting cell apoptosis. The effect of HDL on transplanted adipose-derived stem cells in vivo is largely unknown. Methods: This study focused on exploring the effects of plasma HDL on ADSC and delineating the mechanisms involved in their proliferation after entering the bloodstream. Using the MTT and BrdU assays, we tested the effects of HDL on ADSC proliferation. We probed the downstream intracellular Akt and ERK1/2 signaling pathways and expression of cyclin proteins in ADSC using western blot. Results: Our study found that HDL promotes proliferation of ADSC, by binding to sphingosine-1-phosphate receptor-1(S1P1) on the cell membrane. This interaction led to activation of intracellular Akt and ERK1/2 signaling pathways, resulting in increased expression of cyclin D1 and cyclin E, and simultaneous reduction in expression of cyclin-dependent kinase inhibitors p21 and p27, therefore promoting cell cycle progression and cell proliferation. Conclusions: These studies raise the possibility that HDL may be a physiologic regulator of stem cells and increasing HDL concentrations may be valuable strategy to promote ADSC transplantation.'973' National ST Major Project [2011CB503900]; National Natural Science Foundation of China [81270321, 81170101, 81370235]; Natural Science Foundation of Beijing, China [7122106]SCI(E)[email protected]; [email protected]

Frequency-resolved Raman Thermometry Analysis via a Multi-layer Heat Transfer Model for Bulk and Low-dimensional Materials

Raman thermometry is advantageous for measuring the thermal transport of low-dimensional materials due to its non-contact nature. Transient Raman methods have improved the accuracy of steady-state Raman thermometry by removing the need for accurate temperature calibration and laser absorption evaluation. However, current methods often resort to finite element analysis (FEA) to decipher the measured signals. This step is time-consuming and impedes its ubiquitous adaptation. In this work, we replace the FEA by fitting the transient-state Raman signal to a three-dimensional (3D) analytical heat transfer model for measuring the thermal conductivity of two bulk layered materials [i.e., molybdenum disulfide (MoS2) and bismuth selenide (Bi2Se3) crystals] and the interfacial thermal conductance (h) of CVD-grown MoS2 and molybdenum di-selenide (MoSe2) on quartz (SiO2). Our measured results agree reasonably well with literature and theoretical calculations. We also performed a quantitative sensitivity analysis to give insights on how to improve the measurement sensitivity. Our work provides an efficient way to process the data of transient-based Raman thermometry for high throughput measurements

Large anomalous Hall effect in the kagome ferromagnet LiMn6_6Sn6_6

Kagome magnets are believed to have numerous exotic physical properties due to the possible interplay between lattice geometry, electron correlation and band topology. Here, we report the large anomalous Hall effect in the kagome ferromagnet LiMn$_6$Sn$_6$, which has a Curie temperature of 382 K and easy plane along with the kagome lattice. At low temperatures, unsaturated positive magnetoresistance and opposite signs of ordinary Hall coefficient for $\rho_{xz}$ and $\rho_{yx}$ indicate the coexistence of electrons and holes in the system. A large intrinsic anomalous Hall conductivity of 380 $\Omega^{-1}$ cm$^{-1}$, or 0.44 $e^2/h$ per Mn layer, is observed in $\sigma_{xy}^A$. This value is significantly larger than those in other $R$Mn$_6$Sn$_6$ ($R$ = rare earth elements) kagome compounds. Band structure calculations show several band crossings, including a spin-polarized Dirac point at the K point, close to the Fermi energy. The calculated intrinsic Hall conductivity agrees well with the experimental value, and shows a maximum peak near the Fermi energy. We attribute the large anomalous Hall effect in LiMn$_6$Sn$_6$ to the band crossings closely located near the Fermi energy

Development of vision–based SLAM: from traditional methods to multimodal fusion

Purpose Visual simultaneous localization and mapping (SLAM) has limitations such as sensitivity to lighting changes and lower measurement accuracy. The effective fusion of information from multiple modalities to address these limitations has emerged as a key research focus. This study aims to provide a comprehensive review of the development of vision-based SLAM (including visual SLAM) for navigation and pose estimation, with a specific focus on techniques for integrating multiple modalities. Design/methodology/approach This paper initially introduces the mathematical models and framework development of visual SLAM. Subsequently, this paper presents various methods for improving accuracy in visual SLAM by fusing different spatial and semantic features. This paper also examines the research advancements in vision-based SLAM with respect to multi-sensor fusion in both loosely coupled and tightly coupled approaches. Finally, this paper analyzes the limitations of current vision-based SLAM and provides predictions for future advancements. Findings The combination of vision-based SLAM and deep learning has significant potential for development. There are advantages and disadvantages to both loosely coupled and tightly coupled approaches in multi-sensor fusion, and the most suitable algorithm should be chosen based on the specific application scenario. In the future, vision-based SLAM is evolving toward better addressing challenges such as resource-limited platforms and long-term mapping. Originality/value This review introduces the development of vision-based SLAM and focuses on the advancements in multimodal fusion. It allows readers to quickly understand the progress and current status of research in this field. </jats:sec