The overexpression of TDP-43 in astrocytes causes neurodegeneration via a PTP1B-mediated inflammatory response

Background: Cytoplasmic inclusions of transactive response DNA binding protein of 43 kDa (TDP-43) in neurons and astrocytes are a feature of some neurodegenerative diseases, such as frontotemporal lobar degeneration with TDP-43 (FTLD-TDP) and amyotrophic lateral sclerosis (ALS). However, the role of TDP-43 in astrocyte pathology remains largely unknown. Methods: To investigate whether TDP-43 overexpression in primary astrocytes could induce inflammation, we transfected primary astrocytes with plasmids encoding Gfp or TDP-43-Gfp. The inflammatory response and upregulation of PTP1B in transfected cells were examined using quantitative RT-PCR and immunoblot analysis. Neurotoxicity was analysed in a transwell coculture system of primary cortical neurons with astrocytes and cultured neurons treated with astrocyte-conditioned medium (ACM). We also examined the lifespan, performed climbing assays and analysed immunohistochemical data in pan-glial TDP-43-expressing flies in the presence or absence of a Ptp61f RNAi transgene. Results: PTP1B inhibition suppressed TDP-43-induced secretion of inflammatory cytokines (interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α)) in primary astrocytes. Using a neuron-astrocyte coculture system and astrocyte-conditioned media treatment, we demonstrated that PTP1B inhibition attenuated neuronal death and mitochondrial dysfunction caused by overexpression of TDP-43 in astrocytes. In addition, neuromuscular junction (NMJ) defects, a shortened lifespan, inflammation and climbing defects caused by pan-glial overexpression of TDP-43 were significantly rescued by downregulation of ptp61f (the Drosophila homologue of PTP1B) in flies. Conclusions: These results indicate that PTP1B inhibition mitigates the neuronal toxicity caused by TDP-43-induced inflammation in mammalian astrocytes and Drosophila glial cells. © 2020, The Author(s).1

Enhancement of Near-Infrared Light Absorption via Bottom c-Si Surface Structuring of Perovskite/c-Si Tandem Solar Cells

School of Energy and Chemical Engineering (Energy Engineering)clos

Transparent conducting oxide interlayer-free perovskite/c-Si tandem solar cells

To solve the issues on environmental pollution and depletion of fossil fuels, research for high-efficiency solar cells has been attracted much attention. A tandem solar cell is being considered as a promising device architecture because it is capable of absorbing light in a wide wavelength range by stacking semiconductor materials having different bandgaps. For developing a tandem structure, it is essential to add an interlayer in which photo-induced electrons and holes recombine at the interface of different semiconductor materials. The interlayer should have excellent electrical conductivity for efficient carrier recombination and high transmittance to allow lots of light to reach the lower light absorption layer, simultaneously. Among various materials, Indium tin oxide (ITO) is commonly used as a conventional interlayer. However, the performance of the ITO layer is restricted due to its parasitic light absorption. Hence, it is necessary to develop a material that can replace ITO for the interlayer. In this study, by controlling the temperature condition of the doping process in forming a P-N junction on the front side of the crystalline silicon, a heavily doped emitter of crystalline silicon solar cell having high electrical conductivity was realized and the emitter layer was applied as the interlayer of the perovskite/c-Si tandem solar cell. As a result, the fabricated perovskite/c-Si tandem solar cell exhibited a power conversion efficiency of over 20% with a high filling factor of 82%, which implies that the heavily doped emitter layer would be a very efficient interlayer of tandem structure

N-myc Downstream-Regulated Gene 2 (NDRG2) Function as a Positive Regulator of Apoptosis: A New Insight into NDRG2 as a Tumor Suppressor

N-myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor gene that increases tumor sensitivity to anticancer drugs, slows tumor progression, and inhibits metastasis. NDRG2 is suppressed in various aggressive tumor positions, whereas NDRG2 expression is associated with patient prognosis, such as an improved survival rate. In this review, we summarize the tumor suppressor mechanism of NDRG2 and provide information on the function of NDRG2 concerning the susceptibility of cells to apoptosis. NDRG2 increases the susceptibility to apoptosis in various physiological environments of cells, such as development, hypoxia, nutrient deprivation, and cancer drug treatment. Although the molecular and cell biological mechanisms of NDRG2 have not been fully elucidated, we provide information on the mechanisms of NDRG2 in relation to apoptosis in various environments. This review can assist the design of research regarding NDRG2 function and suggests the potential of NDRG2 as a molecular target for cancer patients

The Function of N-Myc Downstream-Regulated Gene 2 (NDRG2) as a Negative Regulator in Tumor Cell Metastasis

N-myc downstream-regulated gene 2 (NDRG2) is a tumor-suppressor gene that suppresses tumorigenesis and metastasis of tumors and increases sensitivity to anti-cancer drugs. In this review, we summarize information on the clinicopathological characteristics of tumor patients according to NDRG2 expression in various tumor tissues and provide information on the metastasis inhibition-related cell signaling modulation by NDRG2. Loss of NDRG2 expression is a prognostic factor that correlates with TNM grade and tumor metastasis and has an inverse relationship with patient survival in various tumor patients. NDRG2 inhibits cell signaling, such as AKT-, NF-κB-, STAT3-, and TGF-β-mediated signaling, to induce tumor metastasis, and induces activation of GSK-3β which has anti-tumor effects. Although NDRG2 operates as an adaptor protein to mediate the interaction between kinases and phosphatases, which is essential in regulating cell signaling related to tumor metastasis, the molecular mechanism of NDRG2 as an adapter protein does not seem to be fully elucidated. This review aims to assist the research design regarding NDRG2 function as an adaptor protein and suggests NDRG2 as a molecular target to inhibit tumor metastasis and improve the prognosis in tumor patients

A PVT-Robust and Low-Jitter Ring-VCO-Based Injection-Locked Clock Multiplier with a Continuous Frequency-Tracking Loop Using a Replica-Delay Cell and a Dual-Edge Phase Detector

A low-jitter, ring-type voltage-controlled oscillator (VCO)-based injection-locked clock multiplier (ILCM) with a continuous frequency-tracking loop (FTL) for process-voltage-temperature (PVT)-calibration is presented. Using a single replica-delay cell of the VCO that provides the intrinsic phase information of the free-running VCO, the proposed FTL can continuously track and correct frequency drifts. Therefore, the proposed ILCM can calibrate real-time frequency drifts due to voltage or temperature variations as well as static frequency deviations due to process variations. Since the FTL provided an additional filtering of in-band VCO noise, the ILCM was able to achieve excellent jitter performance over the PVT variations, while it was based on a ring-VCO. The proposed ILCM was fabricated in a 65 nm CMOS process. When injection locked, the RMS-jitter integrated from 10 kHz to 40 MHz of the 1.20 GHz output signal was 185 fs. The proposed PVT-calibrator regulated the degradations of jitter to less than 5% and 7% over temperatures and supply voltages, respectively. The active area was $text {0.06 mm}^{2}$ and total power consumption was 9.5 mW.clos

A 320??V-Output Ripple and 90ns-Settling Time at 0.5V Supply Digital-Analog-Hybrid LDO Using Multi-Level Gate-Voltage Generator and Fast-Decision PD Detector

This work presents a digital-analog-hybrid LDO (HLDO) using a multi-level gate-voltage generator (MGG) to achieve a small output ripple (VR) and a fast-transient response. Using the MGG that can partially turn on transistors in the power MOSFET (Mp) and thus reduce Mp's LSB current, VR was limited to less than 320 ??V. Also, a fast-decision PD detector having a non-zero decision level expedited the switching of transistors in Mp, thereby reducing the settling time to less than 90 ns