Potential redox-sensitive Akt activation by dopamine activates Bad and promotes cell death in melanocytes

Dopamine (DA) is a well known oxidative neurotoxin. In addition, Akt has been reported to deliver a survival signal that inhibits apoptosis. However, it has also been reported that chronic Akt activation leads to apoptosis in response to oxidative stress. The objective of the present study was to investigate the possible role of the Akt pathway in vitiligo and its possible relationship with DA-induced cell death using Mel-Ab cells. Cultured Mel-Ab cells were treated with DA with and without N-Acetyl-L-cysteine (NAC), which is known to have antioxidative properties. Cell viability was then assessed by a crystal violet assay and Annexin staining was performed. The changes in the expression of Akt were analyzed by western blot analysis. The cell viability was reduced by approximately 60% in response to treatment with 500 µM DA, and NAC effectively prevented this cytotoxic effect. Likewise, treatment with DA produced numerous Annexin positive cells, while treatment with NAC prevented this apoptotic cell death. Akt was slowly phosphorylated after treatment with DA, while NAC clearly inhibited the DA-induced Akt activation. Western blot analysis also showed that treatment with DA induced the activation of Bad. Finally, LY294002 exerted a protective effect against DA-induced apoptotic cell death. DA may induce redox-sensitive Akt activation and increase the level of Bad, which can promote cell death by heterodimerization with survival proteins. Moreover, NAC effectively protects against DA-induced melanocyte death via inhibition of DA-induced Akt activation

Construction of a DNA Chip for Screening of Genetic Hearing Loss

ObjectivesHearing loss is the most common sensory disorder in humans and genetic causes are estimated to cause more than 50% of all incidents of congenital hearing loss. To develop an efficient method for a genetic diagnosis of hearing loss, we have developed and validated a genetic hearing loss DNA chip that allows the simultaneous analysis of 7 different mutations in the GJB2, SLC26A4, and the mtDNA 12S rRNA genes in Koreans.MethodsA genotyping microarray, based on the allele-specific primer extension (ASPE) method, was used and preliminary validation was examined from the five patients and five controls that were already known their genotypes by DNA sequencing analysis.ResultsThe cutoff Genotyping index (GI) of genotyping for each mutation was set up and validated to discriminate among the genotypes. The result of the DNA chip assay was identical to those of previous results.ConclusionWe successfully designed the genetic hearing loss DNA chip for the first time in Korea and it would be useful for a clinical genetic diagnosis of hearing loss. Further consideration will be needed in order to examine the accuracy of this DNA chip with much larger patient sample numbers

Topical Hypopigmenting Agents for Pigmentary Disorders and Their Mechanisms of Action

Melanin is produced in melanocytes and stored in melanosomes. In spite of its beneficial sun-protective effect, abnormal accumulation of melanin results in esthetic problems. Hydroquinone, competing with tyrosine, is a major ingredient in topical pharmacological agents. However, frequent adverse reactions are amongst its major limitation. To solve this problem, several alternatives such as arbutin, kojic acid, aloesin, and 4-n-butyl resorcinol have been developed. Herein, we classify hypopigmenting agents according to their mechanism of action; a) regulation of enzyme, which is subdivided into three categories, i) regulation of transcription and maturation of tyrosinase, ii) inhibition of tyrosinase activity, and iii) post-transcriptional control of tyrosinase; b) inhibition of melanosome transfer, and c) additional mechanisms such as regulation of the melanocyte environment and antioxidant agents

Reducing time to discovery : materials and molecular modeling, imaging, informatics, and integration

This work was supported by the KAIST-funded Global Singularity Research Program for 2019 and 2020. J.C.A. acknowledges support from the National Science Foundation under Grant TRIPODS + X:RES-1839234 and the Nano/Human Interfaces Presidential Initiative. S.V.K.’s effort was supported by the U.S. Department of Energy (DOE), Office of Science, Basic Energy Sciences (BES), Materials Sciences and Engineering Division and was performed at the Oak Ridge National Laboratory’s Center for Nanophase Materials Sciences (CNMS), a U.S. Department of Energy, Office of Science User Facility.Multiscale and multimodal imaging of material structures and properties provides solid ground on which materials theory and design can flourish. Recently, KAIST announced 10 flagship research fields, which include KAIST Materials Revolution: Materials and Molecular Modeling, Imaging, Informatics and Integration (M3I3). The M3I3 initiative aims to reduce the time for the discovery, design and development of materials based on elucidating multiscale processing-structure-property relationship and materials hierarchy, which are to be quantified and understood through a combination of machine learning and scientific insights. In this review, we begin by introducing recent progress on related initiatives around the globe, such as the Materials Genome Initiative (U.S.), Materials Informatics (U.S.), the Materials Project (U.S.), the Open Quantum Materials Database (U.S.), Materials Research by Information Integration Initiative (Japan), Novel Materials Discovery (E.U.), the NOMAD repository (E.U.), Materials Scientific Data Sharing Network (China), Vom Materials Zur Innovation (Germany), and Creative Materials Discovery (Korea), and discuss the role of multiscale materials and molecular imaging combined with machine learning in realizing the vision of M3I3. Specifically, microscopies using photons, electrons, and physical probes will be revisited with a focus on the multiscale structural hierarchy, as well as structure-property relationships. Additionally, data mining from the literature combined with machine learning will be shown to be more efficient in finding the future direction of materials structures with improved properties than the classical approach. Examples of materials for applications in energy and information will be reviewed and discussed. A case study on the development of a Ni-Co-Mn cathode materials illustrates M3I3's approach to creating libraries of multiscale structure-property-processing relationships. We end with a future outlook toward recent developments in the field of M3I3.Peer reviewe

Hypomorphic Mutations in TONSL Cause SPONASTRIME Dysplasia

SPONASTRIME dysplasia is a rare, recessive skeletal dysplasia characterized by short stature, facial dysmorphism, and aberrant radiographic findings of the spine and long bone metaphysis. No causative genetic alterations for SPONASTRIME dysplasia have yet been determined. Using whole-exome sequencing (WES), we identified bi-allelic TONSL mutations in 10 of 13 individuals with SPONASTRIME dysplasia. TONSL is a multi-domain scaffold protein that interacts with DNA replication and repair factors and which plays critical roles in resistance to replication stress and the maintenance of genome integrity. We show here that cellular defects in dermal fibroblasts from affected individuals are complemented by the expression of wild-type TONSL. In addition, in vitro cell-based as-says and in silico analyses of TONSL structure support the pathogenicity of those TONSL variants. Intriguingly, a knock-in (KI) Tonsl mouse model leads to embryonic lethality, implying the physiological importance of TONSL. Overall, these findings indicate that genetic variants resulting in reduced function of TONSL cause SPONASTRIME dysplasia and highlight the importance of TONSL in embryonic development and postnatal growth.Peer reviewe

Nanoporous NiO plates with a unique role for promoted oxidation of carbonate and carboxylate species in the Li-O2 battery

We report a novel catalytic reaction to promote oxidation of carbonate and carboxylate species using nanoporous nickel oxide (NiO) in the lithium-oxygen (Li-O2) battery. These nanoporous NiO catalysts in the shape of two-dimensional (2-D) hexagonal plates are incorporated on the carbon nanotube (CNT) electrode, which remarkably enhances oxidation efficiency of carbonate and carboxylate species as representative side products in Li-O2 electrochemistry and greatly improves the cycleability to more than 70 cycles. The oxidation reaction predominantly occurs at the nanoporous NiO, toward which the carbonate and carboxylate species may migrate for the complete decomposition. This result is notably distinguished from a NiO-free CNT electrode, where such a passivation layer becomes thicker and precludes electron transfer, thus inducing poor cyclability. © 2015 American Chemical Society154521sciescopu

Nanoporous NiO Plates with a Unique Role for Promoted Oxidation of Carbonate and Carboxylate Species in the Li–O₂ Battery

We report a novel catalytic reaction to promote oxidation of carbonate and carboxylate species using nanoporous nickel oxide (NiO) in the lithium–oxygen (Li–O₂) battery. These nanoporous NiO catalysts in the shape of two-dimensional (2-D) hexagonal plates are incorporated on the carbon nanotube (CNT) electrode, which remarkably enhances oxidation efficiency of carbonate and carboxylate species as representative side products in Li–O₂ electrochemistry and greatly improves the cycleability to more than 70 cycles. The oxidation reaction predominantly occurs at the nanoporous NiO, toward which the carbonate and carboxylate species may migrate for the complete decomposition. This result is notably distinguished from a NiO-free CNT electrode, where such a passivation layer becomes thicker and precludes electron transfer, thus inducing poor cyclability

Biology of melanogenesis and the search for hypopigmenting agents

Increased production and accumulation of melanin are characteristics of a large number of skin diseases, including melasma, post-inflammatory hyperpigmentation and lentigo. A number of clinical agents can reduce normal or abnormal pigmentation, but none of these have achieved satisfactory effects. This review discusses the mechanisms behind the different approaches. Tyrosinase is a pivotal enzyme in melanin synthesis. The majority of whitening or lightening agents act by specifically reducing the activity of tyrosinase via several mechanisms: (1) prior to melanin synthesis (interfering with its transcription and/or glycosylation); (2) during melanin synthesis (tyrosinase inhibition, peroxidase inhibition and reduction of byproducts); and (3) after melanin synthesis (tyrosinase degradation, inhibition of melanosome transfer, acceleration of skin turnover). Additional melanogenesis-associated mechanisms are also discussed