Human Brain Astrocytes Mediate TRAIL-mediated Apoptosis after Treatment with IFN-γ

TNF-related apoptosis inducing ligand (TRAIL) expressions were studied in primary human brain astrocytes in response to pro-inflammatory cytokines. When astrocytes were treated with IL-1β, TNF-α or IFN-γ, TRAIL was induced in cultured fetal astrocytes. In particular, IFN-γ induced the highest levels of TRAIL in cultured astrocytes. When astrocytes were prereated with IFN-γ, they induced apoptosis in TRAIL-sensitive Peer cells. Our results suggest that IFN-γ modulates the expression of TRAIL in astrocytes, which may enhance cytotoxic sensitivity of infiltrating immune cells or brain cells other than astrocytes during inflammation of brain

Compressed Sensing for Elastography in Portable Ultrasound

Bonghun Shin, Soo Jeon, Jeongwon Ryu and Hyock Ju Kwon, “Compressed Sensing for Elastography in Portable Ultrasound,” Ultrasonic Imaging, 39(6), pp. 393-413, Copyright © The Author(s) 2017. Reprinted by permission of SAGE Publications. https://doi.org/10.1177/0161734617716938Portable wireless ultrasound has many advantages such as high portability, easy connectivity, strong individuality, as well as on-site diagnostic ability in real-time. Some of the modern portable ultrasound devices offer high image quality and multiple ultrasound modes comparable to console style ultrasound, however, none of them provides ultrasound elastography function that enables the diagnosis of malignant legions using elastic properties. This is mainly due to the limitations of hardware performance and wireless data transfer speed for processing the large amount of data for elastography. Therefore, reduction of the data transfer size is one of the feasible solutions to overcome these limitations. Recently compressive sensing (CS) theory has been rigorously studied as a means to break the conventional Nyquist sampling rate and thus can significantly decrease the amount of measurement signals without sacrificing signal quality. In this research, we implemented various CS reconstruction frameworks and comparatively evaluated their reconstruction performance for realizing ultrasound elastography function on portable ultrasound. Combinations of three most common model bases (FT, DCT, and WA) and two reconstruction algorithms (l_1 minimization and BSBL) were considered for CS frameworks. Two kinds of numerical phantoms, echoic and elastography phantoms, were developed to evaluate performance of CS on B-mode images and elastograms, respectively. To assess the reconstruction quality, mean absolute error (MAE), signal-to-noise (SNRe) and contrast-to-noise (CNRe) were measured on the B-mode images and elastograms from CS reconstructions. Results suggest that CS reconstruction adopting BSBL algorithm with DCT model basis can yield the best results for all the measures tested, and the maximum data reduction rate for producing readily discernable elastograms is around 60%.Natural Sciences and Engineering Research Council || RGPIN-2015-05273, RGPIN-2015-04118, RGPAS-354703-201

Two novel mutations of Wiskott–Aldrich syndrome: the molecular prediction of interaction between the mutated WASP L101P with WASP-interacting protein by molecular modeling

AbstractWiskott–Aldrich syndrome (WAS) is an X-linked disorder characterized by eczema, thrombocytopenia and increased susceptibility of infections, with mutations of the WAS gene being responsible for WAS and X-linked thrombocytopenia. Herein, two novel mutations of WAS at T336C on exon 3, and at 1326–1329, a G deletion on exon 10, resulting in L101P missense mutation and frameshift mutation 444 stop, respectively, are reported. The affected patients with either mutation showed severe suppression of WAS protein (WASP) levels, T cell proliferation, and CFSE-labeled T cells division. Because WASP L101 have not shown direct nuclear Overhauser effect (NOE) contact with the WASP-interacting protein (WIP) in NMR spectroscopy, molecular modeling was performed to evaluate the molecular effect of WASP P101 to WIP peptide. It is presumed that P101 induced a conformational change in the Q99 residue of WASP and made the side chain of Q99 move away from the WIP peptide, resulting in disruption of the hydrogen bond between Q99 WASP and Y475 WIP. A possible model for the molecular pathogenesis of WAS has been proposed by analyzing the interactions of WASP and WIP using a molecular modeling study

Elastography for Portable Ultrasound

This is a post-peer-review, pre-copyedit version of an article published in Biomedical Engineering Letters. The final authenticated version is available online at https://doi.org/10.1007/s13534-017-0052-1.Portable wireless ultrasound has been emerging as a new ultrasound device due to its unique advantages including small size, lightweight, wireless connectivity and affordability. Modern portable ultrasound devices can offer high quality sonogram images and even multiple ultrasound modes such as color Doppler, echocardiography, and endovaginal examination. However, none of them can provide elastography function yet due to the limitations in computational performance and data transfer speed of wireless communication. Also phase-based strain estimator (PSE) that is commonly used for conventional elastography cannot be adopted for portable ultrasound, because ultrasound parameters such as data dumping interval are varied significantly in the practice of portable ultrasound. Therefore, this research aims to propose a new elastography method suitable for portable ultrasound, called the robust phase-based strain estimator (RPSE), which is not only robust to the variation of ultrasound parameters but also computationally effective. Performance and suitability of RPSE were compared with other strain estimators including time-delay, displacement-gradient and phase-based strain estimators (TSE, DSE and PSE, respectively). Three types of raw RF data sets were used for validation tests: two numerical phantom data sets modeled by an open ultrasonic simulation code (Field II) and a commercial FEA (Abaqus), and the one experimentally acquired with a portable ultrasound device from a gelatin phantom. To assess image quality of elastograms, signal-to-noise (SNRe) and contrast-to-noise (CNRe) ratios were measured on the elastograms produced by each strain estimator. The computational efficiency was also estimated and compared. Results from the numerical phantom experiment showed that RPSE could achieve highest values of SNRe and CNRe (around 5.22 and 47.62 dB) among all strain estimators tested, and almost 10 times higher computational efficiency than TSE and DSE (around 0.06 vs. 5.76 seconds per frame for RPSE and TSE, respectively).Natural Sciences and Engineering Research Council || RGPIN-2015-05273, RGPIN-2015-04118 and RGPAS-354703-201

Ninjurin1 positively regulates osteoclast development by enhancing the survival of prefusion osteoclasts

Osteoclasts (OCs) are bone-resorbing cells that originate from hematopoietic stem cells and develop through the fusion of mononuclear myeloid precursors. Dysregulation of OC development causes bone disorders such as osteopetrosis, osteoporosis, and rheumatoid arthritis. Although the molecular mechanisms underlying osteoclastogenesis have been well established, the means by which OCs maintain their survival during OC development remain unknown. We found that Ninjurin1 (Ninj1) expression is dynamically regulated during osteoclastogenesis and that Ninj1(-/-) mice exhibit increased trabecular bone volume owing to impaired OC development. Ninj1 deficiency did not alter OC differentiation, transmigration, fusion, or actin ring formation but increased Caspase-9-dependent intrinsic apoptosis in prefusion OCs (preOCs). Overexpression of Ninj1 enhanced the survival of mouse macrophage/preOC RAW264.7 cells in osteoclastogenic culture, suggesting that Ninj1 is important for the survival of preOCs. Finally, analysis of publicly available microarray data sets revealed a potent correlation between high NINJ1 expression and destructive bone disorders in humans. Our data indicate that Ninj1 plays an important role in bone homeostasis by enhancing the survival of preOCs

Imidazole-Based Excited-State Intramolecular Proton-Transfer (ESIPT) Materials: Observation of Thermally Activated Delayed Fluorescence (TDF)

We report the first observation of thermally activated delayed fluorescence (TDF) from an excited-state intramolecular proton-transfer (ESIPT) molecule, a hydroxyl-substituted tetraphenyl imidazole derivative (HPI−Ac), in degassed solutions as well as in low-temperature organic matrixes. In the absence of oxygen, the blue emission of an identical spectral feature was observed in the nanosecond (∼4.4 ns) and microsecond (∼25 μs) time domains, and the fluorescence intensity increased with temperature. From the temperature dependence of the time-resolved spectra of HPI−Ac, the energy gap between the first-excited singlet state and the lowest triplet state was determined to be 7.6 ± 0.3 kJ/mol (630 ± 25 cm^(-1)), and the limiting rate constant of intrinsic reverse intersystem crossing was estimated to be 1.3 (±0.5) × 10^7 s^(-1)

Development of Monoclonal Antibodies Against Human IRF-5 and Their Use in Identifying the Binding of IRF-5 to Nuclear Import Proteins Karyopherin-α1 and -β1

PURPOSE: IRF-5 is a direct transducer of virus-mediated and TLR-mediated signaling pathways for the expression of cytokines and chemokines which form homodimers or heterodimers with IRF-7. However, direct IRF-5-specific monoclonal antibodies (mAbs) are not available at present. These could be used to further evaluate the functions of IRF-5. In this study, we produced and characterized three mouse mAbs to human IRF-5. The binding of IRF-5 to nuclear import proteins was first identified using a mAb. MATERIALS AND METHODS: His-tagged human IRF-5 protein spanning amino acid residues 193-257 was used as an antigen and three mAbs were produced. The mAbs were tested with ELISA, Western blot analysis (WB), immunofluorescent staining (IF), and immunoprecipitation (IP). In addition, the nuclear import protein which carried phosphorylated IRF-5 was identified using one of these mAbs. RESULTS: MAbs 5IRF8, 5IRF10 and 5IRF24 which reacted with the recombinant His-IRF-5(193-257) protein were produced. All mAbs bound to human IRF-5, but not to IRF-3 or IRF-7. They could be used for WB, IF, and IP studies. The binding of phosphorylated IRF-5 to karyopherin-alpha1 and -beta1 was also identified. CONCLUSION: Human IRF-5-specific mAbs are produced for studying the immunologic roles related to IRF-5. Phosphorylated IRF-5 is transported to the nucleus by binding to nuclear import proteins karyopherin-alpha1 and -beta1.ope

Diagnosis in a Preclinical Model of Bladder Pain Syndrome Using a Au/ZnO Nanorod-based SERS Substrate

To evaluate the feasibility of ZnO nanorod-based surface enhanced Raman scattering (SERS) diagnostics for disease models, particularly for interstitial cystitis/bladder pain syndrome (IC/BPS), ZnO-based SERS sensing chips were developed and applied to an animal disease model. ZnO nanorods were grown to form nano-sized porous structures and coated with gold to facilitate size-selective biomarker detection. Raman spectra were acquired on a surface enhanced Raman substrate from the urine in a rat model of IC/BPS and analyzed using a statistical analysis method called principal component analysis (PCA). The nanorods grown after the ZnO seed deposition were 30 to 50 nm in diameter and 500 to 600 nm in length. A volume of gold corresponding to a thin film thickness of 100 nm was deposited on the grown nanorod structure. Raman spectroscopic signals were measured in the scattered region for nanometer biomarker detection to indicate IC/BPS. The Raman peaks for the control group and IC/BPS group are observed at 641, 683, 723, 873, 1002, 1030, and 1355 cm(-1),which corresponded to various bonding types and compounds. The PCA results are plotted in 2D and 3D. The Raman signals and statistical analyses obtained from the nano-sized biomarkers of intractable inflammatory diseases demonstrate the possibility of an early diagnosis

Regulation of the Catabolic Cascade in Osteoarthritis by the Zinc-ZIP8-MTF1 Axis

SummaryOsteoarthritis (OA), primarily characterized by cartilage degeneration, is caused by an imbalance between anabolic and catabolic factors. Here, we investigated the role of zinc (Zn2+) homeostasis, Zn2+ transporters, and Zn2+-dependent transcription factors in OA pathogenesis. Among Zn2+ transporters, the Zn2+ importer ZIP8 was specifically upregulated in OA cartilage of humans and mice, resulting in increased levels of intracellular Zn2+ in chondrocytes. ZIP8-mediated Zn2+ influx upregulated the expression of matrix-degrading enzymes (MMP3, MMP9, MMP12, MMP13, and ADAMTS5) in chondrocytes. Ectopic expression of ZIP8 in mouse cartilage tissue caused OA cartilage destruction, whereas Zip8 knockout suppressed surgically induced OA pathogenesis, with concomitant modulation of Zn2+ influx and matrix-degrading enzymes. Furthermore, MTF1 was identified as an essential transcription factor in mediating Zn2+/ZIP8-induced catabolic factor expression, and genetic modulation of Mtf1 in mice altered OA pathogenesis. We propose that the zinc-ZIP8-MTF1 axis is an essential catabolic regulator of OA pathogenesis