Art as Meaning Making

This project examines the meaning-making of art through multiple disciplinary lenses: Art Therapy, Art History, Studio Art, Art Education and Anthropology. Disciplines were selected for their inherent ability to enhance an understanding of meaning-making through the art making process and art product. An arts-based methodology was utilized in conjunction with the Outliers and American Vanguard Art exhibition at The Los Angeles County Museum of Art (LACMA), which featured a juxtaposition of formally trained and self-taught artists. Each of the five researchers selected a piece of art included in the exhibition, rendered the piece, documented the rendering process, and viewed each piece and its accompanying documentation from their respective disciplinary lenses to understand meaning-making of the original artist and their work. Results of this systematic investigation exposed common themes across disciplines that inform meaning-making: Culture, Context, Comparison, Communication, Formal Elements, and Accuracy. Through an understanding of elements that comprise each exposed theme, the discipline of art therapy can expand its theoretical and practical knowledge that currently informs its approaches toward the meaning-making of art. Results of this arts-based investigation imply that continued investigation of adjacent art and culture-centric disciplines can question, corroborate, and supplement existing assumptions about the meaning-making of art process and art product in the discipline of art therapy

Treatment of Branch Retinal Artery Occlusion With Transluminal Nd:YAG Laser Embolysis

The purpose of this paper was to report a successful treatment of transluminal Nd:YAG laser embolysis (NYE) for branch retinal artery occlusion (BRAO) with visible emboli. Two patients with acute, severe vision loss secondary to a branch retinal artery occlusion with visible emboli in one eye underwent NYE. A complete ocular examination was performed which included biomicroscopy of the posterior pole of the retina, intraocular pressure measurement, fundus color photographs, and fluorescein angiography (FA). After the NYE, the two patients showed dramatic improvements in best-corrected visual acuity, as well as, immediate and dramatic restorations in flow past the obstructed arteriole in FA. NYE is a treatment modality to be considered in patients with BRAO who present acutely with severe vision loss and a visible embolus

Matrix Metalloproteinase-3 Causes Dopaminergic Neuronal Death through Nox1-Regenerated Oxidative Stress

In the present study we investigated the interplay between matrix metalloproteinase 3 (MMP3) and NADPH oxidase 1 (Nox1) in the process of dopamine (DA) neuronal death. We found that MMP3 activation causes the induction of Nox1 via mitochondrial reactive oxygen species (ROS) production and subsequently Rac1 activation, eventually leading to Nox1-derived superoxide generation in a rat DA neuronal N27 cells exposed to 6-OHDA. While a MMP3 inhibitor, NNGH, largely attenuated mitochondrial ROS and subsequent Nox1 induction, both apocynin, a putative Nox inhibitor and GKT137831, a Nox1 selective inhibitor failed to reduce 6-OHDA-induced mitochondrial ROS. However, both inhibitors for MMP3 and Nox1 similarly attenuated 6-OHDA-induced N27 cell death. RNAi-mediated selective inhibition of MMP3 or Nox1 showed that knockdown of either MMP3 or Nox1 significantly reduced 6-OHDA-induced ROS generation in N27 cells. While 6-OHDA-induced Nox1 was abolished by MMP3 knockdown, Nox1 knockdown did not alter MMP3 expression. Direct overexpression of autoactivated MMP3 (actMMP3) in N27 cells or in rat substantia nigra (SN) increased expression of Nox1. Selective knockdown of Nox1 in the SN achieved by adeno-associated virus-mediated overexpression of Nox1-specific shRNA largely attenuated the actMMP3-mediated dopaminergic neuronal loss. Furthermore, Nox1 expression was significantly attenuated in Mmp3 null mice treated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Together we established novel molecular mechanisms underlying oxidative stress-mediated dopaminergic neuronal death in which MMP3 activation is a key upstream event that leads to mitochondrial ROS, Nox1 induction and eventual dopaminergic neuronal death. Our findings may lead to the development of novel therapeutic approach

Matrix Metalloproteinase-3 Causes Dopaminergic Neuronal Death through Nox1-Regenerated Oxidative Stress

In the present study we investigated the interplay between matrix metalloproteinase 3 (MMP3) and NADPH oxidase 1 (Nox1) in the process of dopamine (DA) neuronal death. We found that MMP3 activation causes the induction of Nox1 via mitochondrial reactive oxygen species (ROS) production and subsequently Rac1 activation, eventually leading to Nox1-derived superoxide generation in a rat DA neuronal N27 cells exposed to 6-OHDA. While a MMP3 inhibitor, NNGH, largely attenuated mitochondrial ROS and subsequent Nox1 induction, both apocynin, a putative Nox inhibitor and GKT137831, a Nox1 selective inhibitor failed to reduce 6-OHDA-induced mitochondrial ROS. However, both inhibitors for MMP3 and Nox1 similarly attenuated 6-OHDA-induced N27 cell death. RNAi-mediated selective inhibition of MMP3 or Nox1 showed that knockdown of either MMP3 or Nox1 significantly reduced 6-OHDA-induced ROS generation in N27 cells. While 6-OHDA-induced Nox1 was abolished by MMP3 knockdown, Nox1 knockdown did not alter MMP3 expression. Direct overexpression of autoactivated MMP3 (actMMP3) in N27 cells or in rat substantia nigra (SN) increased expression of Nox1. Selective knockdown of Nox1 in the SN achieved by adeno-associated virus-mediated overexpression of Nox1-specific shRNA largely attenuated the actMMP3-mediated dopaminergic neuronal loss. Furthermore, Nox1 expression was significantly attenuated in Mmp3 null mice treated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Together we established novel molecular mechanisms underlying oxidative stress-mediated dopaminergic neuronal death in which MMP3 activation is a key upstream event that leads to mitochondrial ROS, Nox1 induction and eventual dopaminergic neuronal death. Our findings may lead to the development of novel therapeutic approach

Accelerated System-Level Seismic Risk Assessment of Bridge Transportation Networks through Artificial Neural Network-Based Surrogate Model

Featured Application Post-hazard flow capacity of the lifeline network and recovery strategy against natural disaster. In this study, an artificial neural network (ANN)-based surrogate model is proposed to evaluate the system-level seismic risk of bridge transportation networks efficiently. To estimate the performance of a network, total system travel time (TSTT) was introduced as a performance index, and an ANN-based surrogate model was incorporated to evaluate a high-dimensional network with probabilistic seismic hazard analysis (PSHA) efficiently. To generate training data, the damage states of bridge components were considered as the input training data, and TSTT was selected as output data. An actual bridge transportation network in South Korea was considered as the target network, and the entire network map was reconstructed based on geographic information system data to demonstrate the proposed method. For numerical analysis, the training data were generated based on epicenter location history. By using the surrogate model, the network performance was estimated for various earthquake magnitudes at the trained epicenter with significantly-reduced computational time cost. In addition, 20 historical epicenters were adopted to confirm the robustness of the epicenter. Therefore, it was concluded that the proposed ANN-based surrogate model could be used as an alternative for efficient system-level seismic risk assessment of high-dimensional bridge transportation networks

Dimeric configuration of SeqA protein bound to a pair of hemi-methylated GATC sequences

The binding of SeqA protein to hemi-methylated GATC sequences (hemi-sites) regulates chromosome initiation and the segregation of replicated chromosome in Escherichia coli. We have used atomic force microscopy to examine the architecture of SeqA and the mode of binding of one molecule of SeqA to a pair of hemi-sites in aqueous solution. SeqA has a bipartite structure composed of a large and a small lobe. Upon binding of a SeqA molecule to a pair of hemi-sites, the larger lobe becomes visibly separated into two DNA binding domains, each of which binds to one hemi-site. The two DNA binding domains are held together by association between the two multimerization domains that make up the smaller lobe. The binding of each DNA binding domain to a hemi-site leads to bending of the bound DNA inwards toward the bound protein. In this way, SeqA adopts a dimeric configuration when bound to a pair of hemi-sites. Mutational analysis of the multimerization domain indicates that, in addition to multimerization of SeqA polypeptides, this domain contributes to the ability of SeqA to bind to a pair of hemi-sites and to its cooperative behavior

Current advances in combining stem cell and gene therapy for neurodegenerative diseases

Neuronal death is the common final pathologic pathway of various neurodegenerative diseases (NDs). Although central nervous system has little regenerative potential, it is expected that damaged neural tissue can be recovered by exogenous supplementation of stem cells; however, stem cell therapy cannot modulate specific causes of NDs, such as accumulation of extracellular amyloid peptides in Alzheimer’s disease. In contrast, gene therapy can deliver therapeutic genes to specific ND targets. Therefore, combining stem cell and gene therapy would have dual treatment mechanisms (regenerating damaged neural tissue and modifying specific causes of NDs) and lead to better clinical outcomes. In this review, we discuss various therapeutic genes that can be used to develop stem cell gene therapy for various NDs and the techniques for how therapeutic genes can be integrated into stem cells

Taurine in drinking water recovers learning and memory in the adult APP/PS1 mouse model of Alzheimer's disease

Alzheimer's disease (AD) is a lethal progressive neurological disorder affecting the memory. Recently, US Food and Drug Administration mitigated the standard for drug approval, allowing symptomatic drugs that only improve cognitive deficits to be allowed to accelerate on to clinical trials. Our study focuses on taurine, an endogenous amino acid found in high concentrations in humans. It has demonstrated neuroprotective properties against many forms of dementia. In this study, we assessed cognitively enhancing property of taurine in transgenic mouse model of AD. We orally administered taurine via drinking water to adult APP/PS1 transgenic mouse model for 6 weeks. Taurine treatment rescued cognitive deficits in APP/PS1 mice up to the age-matching wild-type mice in Y-maze and passive avoidance tests without modifying the behaviours of cognitively normal mice. In the cortex of APP/PS1 mice, taurine slightly decreased insoluble fraction of Aβ. While the exact mechanism of taurine in AD has not yet been ascertained, our results suggest that taurine can aid cognitive impairment and may inhibit Aβ-related damages.MIT International Science and Technology InitiativesKorea Health Industry Development Institute (H14C04660000)Korea Institute of Science and Technology (Open Research 2E24582)Korea Institute of Science and Technology (Flagship 2E25023

A Novel Selective Sphingosine Kinase 2 Inhibitor, HWG-35D, Ameliorates the Severity of Imiquimod-Induced Psoriasis Model by Blocking Th17 Differentiation of Naïve CD4 T Lymphocytes

Sphingosine kinases (SK) catalyze the phosphorylation of sphingosine to generate sphingosine-1-phosphate. Two isoforms of SK (SK1 and SK2) exist in mammals. Previously, we showed the beneficial effects of SK2 inhibition, using ABC294640, in a psoriasis mouse model. However, ABC294640 also induces the degradation of SK1 and dihydroceramide desaturase 1 (DES1). Considering these additional effects of ABC294640, we re-examined the efficacy of SK2 inhibition in an IMQ-induced psoriasis mouse model using a novel SK2 inhibitor, HWG-35D, which exhibits nM potency and 100-fold selectivity for SK2 over SK1. Topical application of HWG-35D ameliorated IMQ-induced skin lesions and normalized the serum interleukin-17A levels elevated by IMQ. Application of HWG-35D also decreased skin mRNA levels of interleukin-17A, K6 and K16 genes induced by IMQ. Consistent with the previous data using ABC294640, HWG-35D also blocked T helper type 17 differentiation of naive CD4+ T cells with concomitant reduction of SOCS1. Importantly, HWG-35D did not affect SK1 or DES1 expression levels. These results reaffirm an important role of SK2 in the T helper type 17 response and suggest that highly selective and potent SK2 inhibitors such as HWG-35D might be of therapeutic use for the treatment of psoriasis