New and Notable This Week

This week’s selection of recently published papers from MDPI journals.


A Compact Microelectrode Array Chip with Multiple Measuring Sites for Electrochemical Applications

Maria Dimaki 1,, Marco Vergani 2, Arto Heiskanen 1, Dorota Kwasny 1, Luigi Sasso 1,3, Marco Carminati 2, Juliet A. Gerrard 3, Jenny Emneus 1 and Winnie E. Svendsen1

1DTU Nanotech, Technical University of Denmark, Oersteds Plads, Bldg 345E, 2800 Kgs. Lyngby, Denmark, 2Dipartimento di Elettronica e Informazione, Politecnico di Milano, Piazza Leonardo da Vinci 32, I-20133 Milano, Italy, 3The MacDiarmid Institute for Advanced Materials and Nanotechnology, Biomolecular Interaction Centre, School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand

Abstract: In this paper we demonstrate the fabrication and electrochemical characterization of a microchip with 12 identical but individually addressable electrochemical measuring sites, each consisting of a set of interdigitated electrodes acting as a working electrode as well as two circular electrodes functioning as a counter and reference electrode in close proximity. The electrodes are made of gold on a silicon oxide substrate and are passivated by a silicon nitride membrane. A method for avoiding the creation of high edges at the electrodes (known as lift-off ears) is presented. The microchip design is highly symmetric to accommodate easy electronic integration and provides space for microfluidic inlets and outlets for integrated custom-made microfluidic systems on top .


For Open Access Article, see: Dimaki, M.; Vergani, M.; Heiskanen, A.; Kwasny, D.; Sasso, L.; Carminati, M.; Gerrard, J.A.; Emneus, J.; Svendsen, W.E. A Compact Microelectrode Array Chip with Multiple Measuring Sites for Electrochemical ApplicationsSensors 201414, 9505-9521.



Zn-Driven Discovery of a Hydrothermal Vent Fungal Metabolite Clavatustide C, and an Experimental Study of the Anti-Cancer Mechanism of Clavatustide B

Panpan Ye 1, Ling Shen 1, Wei Jiang 2, Ying Ye 2, Chen-Tung Arthur Chen 2,3, Xiaodan Wu 2, Kuiwu Wang 4 and Bin Wu 2

1Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China2 Ocean College, Zhejiang University, Hangzhou 310058, China, 3Institute of Marine Geology and Chemistry, National Sun Yat-sen University, Kaohsiung 80424, Taiwan, 4Department of Applied Chemistry, Zhejiang Gongshang University, Hangzhou 310058, China

Abstract: A naturally new cyclopeptide, clavatustide C, was produced as a stress metabolite in response to abiotic stress elicitation by one of the hydrothermal vent fluid components Zn in the cultured mycelia of Aspergillus clavatusC2WU, which were isolated from Xenograpsus testudinatusX. testudinatus lives at extreme, toxic habitat around the sulphur-rich hydrothermal vents in Taiwan Kueishantao. The known compound clavatustide B was also isolated and purified. This is the first example of a new hydrothermal vent microbial secondary metabolite produced in response to abiotic Zn treatment. The structures were established by spectroscopic means. The regulation of G1-S transition in hepatocellular carcinoma cell lines by clavatustide B was observed in our previous study. The purpose of the present study was to verify these results in other types of cancer cell lines and elucidate the possible molecular mechanism for the anti-cancer activities of clavatustide B. In different human cancer cell lines, including pancreatic cancer (Panc-1), gastric cancer (MGC-803), colorectal cancer (SW-480), retinoblastoma (WERI-Rb-1) and prostate cancer (PC3), clavatustide B efficiently suppressed cell proliferations in a dose-dependent manner. Although different cancer cell lines presented variety in Max effect dose and IC50 dose, all cancer cell lines showed a lower Max effect dose and IC50 dose compared with human fibroblasts (hFB) (p < 0.05). Moreover, significant accumulations in G1 phases and a reduction in S phases (p < 0.05) were observed under clavatustide B treatment. The expression levels of 2622 genes including 39 cell cycle-associated genes in HepG2 cells were significantly altered by the treatment with 15 μg/mL clavatustide B after 48 h. CCNE2 (cyclin E2) was proved to be the key regulator of clavatustide B-induced G1-S transition blocking in several cancer cell lines by using real-time PCR.


For Open Access Article, see: Ye, P.; Shen, L.; Jiang, W.; Ye, Y.; Chen, C.-T.A.; Wu, X.; Wang, K.; Wu, B. Zn-Driven Discovery of a Hydrothermal Vent Fungal Metabolite Clavatustide C, and an Experimental Study of the Anti-Cancer Mechanism of Clavatustide BMar. Drugs 201412, 3203-3217.



A Compact Immunoassay Platform Based on a Multicapillary Glass Plate

Shuhua Xue, Hulie Zeng, Jianmin Yang, Hizuru Nakajima  and Katsumi Uchiyama

Department of Applied Chemistry, Graduate School of Urban Environmental Sciences, Tokyo Metropolitan University, 1-1 Minamiohsawa, Hachioji, Tokyo 192-0397, Japan

Abstract: A highly sensitive, rapid immunoassay performed in the multi-channels of a micro-well array consisting of a multicapillary glass plate (MCP) and a polydimethylsiloxane (PDMS) slide is described. The micro-dimensions and large surface area of the MCP permitted the diffusion distance to be decreased and the reaction efficiency to be increased. To confirm the concept of the method, human immunoglobulin A (h-IgA) was measured using both the proposed immunoassay system and the traditional 96-well plate method. The proposed method resulted in a 1/5-fold decrease of immunoassay time, and a 1/56-fold cut in reagent consumption with a 0.05 ng/mL of limit of detection (LOD) for IgA. The method was also applied to saliva samples obtained from healthy volunteers. The results correlated well to those obtained by the 96-well plate method. The method has the potential for use in disease diagnostic or on-site immunoassays.


For Open Access Article, see: Xue, S.; Zeng, H.; Yang, J.; Nakajima, H.; Uchiyama, K. A Compact Immunoassay Platform Based on a Multicapillary Glass PlateSensors 201414, 9132-9144.



Involvement of HDAC1 and HDAC3 in the Pathology of Polyglutamine Disorders: Therapeutic Implications for Selective HDAC1/HDAC3 Inhibitors

Elizabeth A. Thomas

Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, SP2030 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA

Abstract: Histone deacetylases (HDACs) enzymes, which affect the acetylation status of histones and other important cellular proteins, have been recognized as potentially useful therapeutic targets for a broad range of human disorders. Emerging studies have demonstrated that different types of HDAC inhibitors show beneficial effects in various experimental models of neurological disorders. HDAC enzymes comprise a large family of proteins, with18 HDAC enzymes currently identified in humans. Hence, an important question for HDAC inhibitor therapeutics is which HDAC enzyme(s) is/are important for the amelioration of disease phenotypes, as it has become clear that individual HDAC enzymes play different biological roles in the brain. This review will discuss evidence supporting the involvement of HDAC1 and HDAC3 in polyglutamine disorders, including Huntington’s disease, and the use of HDAC1- and HDAC3-selective HDAC inhibitors as therapeutic intervention for these disorders. Further, while HDAC inhibitors are known alter chromatin structure resulting in changes in gene transcription, understanding the exact mechanisms responsible for the preclinical efficacy of these compounds remains a challenge. The potential chromatin-related and non-chromatin-related mechanisms of action of selective HDAC inhibitors will also be discussed.


For Open Access Article, see: Thomas, E.A. Involvement of HDAC1 and HDAC3 in the Pathology of Polyglutamine Disorders: Therapeutic Implications for Selective HDAC1/HDAC3 InhibitorsPharmaceuticals 20147, 634-661.



Keratoacanthoma Pathobiology in Mouse Models

Katherine N. Gibson-Corley 1, Laura M. Rogers 2, Adam Goeken 1, Adam J. Dupuy 3 and David K. Meyerholz 1

1Department of Pathology, University of Iowa, Iowa City, IA 52242, USA, 2Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA, 3Department of Anatomy & Cell Biology, Roy J. & Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA

Abstract: Recently we described skin tumors driven by skin-specific expression of Zmiz1 and here we define keratoacanthoma pathobiology in this mouse model. Similar to human keratoacanthoma development, we were able to segregate murine keratoacanthomas into three developmental phases: growth, maturation, and regression. These tumors had areas with cellular atypia, high mitotic rate, and minor local invasion in the growth phase, but with development they transitioned to maturation and regression phases with evidence of resolution. The early aggressive appearance could easily be misdiagnosed as a malignant change if the natural pathobiology was not well-defined in the model. To corroborate these findings in the Zmiz1 model, we examined squamous skin tumors from another tumor study in aging mice, and these tumors followed a similar biological progression. Lastly, we were able to evaluate the utility of the model to assess immune cell infiltration (F4/80, B220 Granzyme B, CD3 cells, arginase-1) in the regression phase; however, because inflammation was present at all phases of development, a more comprehensive approach will be needed in future investigations. Our study of keratoacanthomas in selected murine models suggests that these squamous tumors can appear histologically aggressive during early development, but with time will enter a regression phase indicating a benign biology. Importantly, studies of squamous skin tumor models should be cautious in tumor diagnosis as the early growth distinction between malignant versus benign based solely on histopathology may not be easily discerned without longitudinal studies to confirm the tumor pathobiology.


For Open Access Article, see: Gibson-Corley, K.N.; Rogers, L.M.; Goeken, A.; Dupuy, A.J.; Meyerholz, D.K. Keratoacanthoma Pathobiology in Mouse ModelsDiseases 20142, 106-119.