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14 pages, 2716 KB

Open AccessArticle

Accurate Prediction of Transcriptional Activity of Single Missense Variants in HIV Tat with Deep Learning

by Houssemeddine Derbel, Christopher J. Giacoletto, Ronald Benjamin, Gordon Chen, Martin R. Schiller and Qian Liu

Int. J. Mol. Sci. 2023, 24(7), 6138; https://doi.org/10.3390/ijms24076138 - 24 Mar 2023

Cited by 3 | Viewed by 3180

Abstract

Tat is an essential gene for increasing the transcription of all HIV genes, and affects HIV replication, HIV exit from latency, and AIDS progression. The Tat gene frequently mutates in vivo and produces variants with diverse activities, contributing to HIV viral heterogeneity as well as drug-resistant clones. Thus, identifying the transcriptional activities of Tat variants will help to better understand AIDS pathology and treatment. We recently reported the missense mutation landscape of all single amino acid Tat variants. In these experiments, a fraction of double missense alleles exhibited intragenic epistasis. However, it is too time-consuming and costly to determine the effect of the variants for all double mutant alleles through experiments. Therefore, we propose a combined GigaAssay/deep learning approach. As a first step to determine activity landscapes for complex variants, we evaluated a deep learning framework using previously reported GigaAssay experiments to predict how transcription activity is affected by Tat variants with single missense substitutions. Our approach achieved a 0.94 Pearson correlation coefficient when comparing the predicted to experimental activities. This hybrid approach can be extensible to more complex Tat alleles for a better understanding of the genetic control of HIV genome transcription. Full article

(This article belongs to the Special Issue Recent Advances in Human Genetics)

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9 pages, 1095 KB

Open AccessArticle

Switchable Interfaces: Redox Monolayers on Si(100) by Electrochemical Trapping of Alcohol Nucleophiles

by Long Zhang, Ruth Belinda Domínguez Espíndola, Benjamin B. Noble, Vinicius R. Gonçales, Gordon G. Wallace, Nadim Darwish, Michelle L. Coote and Simone Ciampi

Surfaces 2018, 1(1), 3-11; https://doi.org/10.3390/surfaces1010002 - 20 Jul 2018

Cited by 15 | Viewed by 5285

Abstract

Organic electrosynthesis is going through its renaissance but its scope in surface science as a tool to introduce specific molecular signatures at an electrode/electrolyte interface is under explored. Here, we have investigated an electrochemical approach to generate in situ surface-tethered and highly-reactive carbocations. We have covalently attached an alkoxyamine derivative on an Si(100) electrode and used an anodic bias stimulus to trigger its fragmentation into a diffusive nitroxide (TEMPO) and a surface-confined carbocation. As a proof-of-principle we have used this reactive intermediate to trap a nucleophile dissolved in the electrolyte. The nucleophile was ferrocenemethanol and its presence and surface concentration after its reaction with the carbocation were assessed by cyclic voltammetry. The work expands the repertoire of available electrosynthetic methods and could in principle lay the foundation for a new form of electrochemical lithography. Full article

(This article belongs to the Special Issue Electrochemical Surface Science: Basics and Applications)

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17 pages, 4149 KB

Open AccessReview

Transition Metal Intercalators as Anticancer Agents—Recent Advances

by Krishant M. Deo, Benjamin J. Pages, Dale L. Ang, Christopher P. Gordon and Janice R. Aldrich-Wright

Int. J. Mol. Sci. 2016, 17(11), 1818; https://doi.org/10.3390/ijms17111818 - 31 Oct 2016

Cited by 87 | Viewed by 11808

Abstract

The diverse anticancer utility of cisplatin has stimulated significant interest in the development of additional platinum-based therapies, resulting in several analogues receiving clinical approval worldwide. However, due to structural and mechanistic similarities, the effectiveness of platinum-based therapies is countered by severe side-effects, narrow spectrum of activity and the development of resistance. Nonetheless, metal complexes offer unique characteristics and exceptional versatility, with the ability to alter their pharmacology through facile modifications of geometry and coordination number. This has prompted the search for metal-based complexes with distinctly different structural motifs and non-covalent modes of binding with a primary aim of circumventing current clinical limitations. This review discusses recent advances in platinum and other transition metal-based complexes with mechanisms of action involving intercalation. This mode of DNA binding is distinct from cisplatin and its derivatives. The metals focused on in this review include Pt, Ru and Cu along with examples of Au, Ni, Zn and Fe complexes; these complexes are capable of DNA intercalation and are highly biologically active. Full article

(This article belongs to the Special Issue Recent Advances in Metal Based Drugs)

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23 pages, 367 KB

Open AccessReview

Symbiodinium—Invertebrate Symbioses and the Role of Metabolomics

by Benjamin R. Gordon and William Leggat

Mar. Drugs 2010, 8(10), 2546-2568; https://doi.org/10.3390/md8102546 - 30 Sep 2010

Cited by 118 | Viewed by 20990

Abstract

Symbioses play an important role within the marine environment. Among the most well known of these symbioses is that between coral and the photosynthetic dinoflagellate, Symbiodinium spp. Understanding the metabolic relationships between the host and the symbiont is of the utmost importance in order to gain insight into how this symbiosis may be disrupted due to environmental stressors. Here we summarize the metabolites related to nutritional roles, diel cycles and the common metabolites associated with the invertebrate-Symbiodinium relationship. We also review the more obscure metabolites and toxins that have been identified through natural products and biomarker research. Finally, we discuss the key role that metabolomics and functional genomics will play in understanding these important symbioses. Full article

(This article belongs to the Special Issue Metabolomic Approaches to Marine Organisms)

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