Biochemistry Commons^™

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …

Copper(Ii) And Silver(I)‑1,10‑Phenanthroline‑5,6‑Dione Complexes Interact With Double‑Stranded Dna: Further Evidence Of Their Apparent Multi‑Modal Activity Towards Pseudomonas Aeruginosa, Anna Clara Milesi Galdino, Lívia Viganor, Matheus Mendonça Pereira, Michael Devereux, Malachy Mccann, Marta Helena Branquinha, Zara Molphy, Sinéad O'Carroll, Conor Bain, Georgia Menounou, Andrew Kellett, André Luis Souza Dos Santos

Articles

Tackling microbial resistance requires continuous efforts for the development of new molecules with novel mechanisms of action and potent antimicrobial activity. Our group has previously identified metal-based compounds, [Ag(1,10-phenanthroline-5,6-dione)2]ClO4 (Ag-phendione) and [Cu(1,10-phenanthroline-5,6-dione)3](ClO4)2.4H2O (Cu-phendione), with efficient antimicrobial action against multidrug-resistant species. Herein, we investigated the ability of Ag-phendione and Cu-phendione to bind with double-stranded DNA using a combination of in silico and in vitro approaches. Molecular docking revealed that both phendione derivatives can interact with the DNA by hydrogen bonding, hydrophobic and electrostatic interactions. Cu-phendione exhibited the highest binding affinity to either major (− 7.9 kcal/mol) or minor (− 7.2 kcal/mol) …

Multicomponent Analysis Using A Confocal Raman Microscope, Zhengyuan Tang, Sinead J. Barton, Thomas E. Ward, John P. Lowry, Michelle M. Doran, Hugh Byrne, Bryan M. Hennelly

Articles

Measuring the concentration of multiple chemical components in a low volume aqueous mixture by Raman spectroscopy has received significant interest in the literature. All of the contributions to date focus on the design of optical systems that facilitate the recording of spectra with high signal-to-noise ratio, by collecting as many Raman scattered photons as possible. In this study, the confocal Raman microscope set-up is investigated for multicomponent analysis. Partial Least Squares Regression is used to quantify physiologically relevant aqueous mixtures of glucose, lactic acid, and urea. The predicted error is 17.81 mg/dL for glucose, 10.6 mg/dL for lactic acid and …

Raman Spectral Analysis For Rapid Screening Of Dengue Infection, Tahir Mahmood, Haq Nawaz, A. Ditta, M.I. Majeed, M.A. Hanif, N. Rashid, H.N. Bhatti, H.F. Nargis, M. Saleem, Franck Bonnier, Hugh Byrne

Articles

Infection with the dengue virus is currently clinically detected according to different biomarkers in human blood plasma, commonly measured by enzyme linked immunosorbent assays, including non-structural proteins (Ns1), immunoglobulin M (IgM) and immunoglobulin G (IgG). However, there is little or no mutual correlation between the biomarkers, as demonstrated in this study by a comparison of their levels in samples from 17 patients. As an alternative, the label free, rapid screening technique, Raman spectroscopy has been used for the characterisation/diagnosis of healthy and dengue infected human blood plasma samples. In dengue positive samples, changes in specific Raman spectral bands associated with …

In Vitro Label Free Screening Of Chemotherapeutic Drugs Using Raman Micro-Spectroscopy: Towards A New Paradigm Of Spectralomics., Zeineb Farhane, Haq Nawaz, Franck Bonnier, Hugh Byrne

Articles

This overview groups some of the recent studies highlighting the potential application of Raman micro-spectroscopy as an analytical technique in preclinical development to predict drug mechanism of action and in clinical application as a companion diagnostic and in personalised therapy due to its capacity to predict cellular resistance and therefore to optimise chemotherapeutic treatment efficacy.

Notably, the anthracyclines, Doxorubicin and Actinomycin D, elicit similar spectroscopic signatures of subcellular interaction characteristic of the mode of action of intercalation. Although Cisplatin and Vincristine show markedly different signatures, at low exposure doses, their signatures at higher doses show marked similarities to those elicited …

A Conceptual Framework For Understanding The Biogeochemistry Of Dry Riverbeds Through The Lens Of Soil Science, Maria Isabel Arce, Clara Mendoza, Maria Almagro, Nuria Catalan, Anna M. Romani, Eugenia Marti, R. Gomez, Susana Bernal, Arnaud Foulquier, Michael Mutz, Rafael Marce, Annamaria Zoppini, Giulia Gionchetta, Gabriele Weigelhofer, R. Del Campo, Christopher T. Robinson, Alan Gilmer, Martin Rulik, Obrador Biel, Oleksandra Shumilova, Sanja Zlatanovic, Shai Arnon, Petr Baldrian, Gabriel Andreas Singer, Thibault Datry, Nikolaos Th Skoulikidis, Britta Tietjen, Daniel Von Schiller

Articles

Intermittent rivers and ephemeral streams (IRES) encompass fluvial ecosystems that eventually stop flowing and run dry at some point in space and time. During the dry phase, channels of IRES consist mainly of dry riverbeds (DRBs), prevalent yet widely unexplored ecotones between dry and wet phases that can strongly influence the biogeochemistry of fluvial networks. DRBs are often overlooked because they do not strictly belong to either domain of soil or freshwater science. Due to this dual character of DRBs, we suggest that concepts and knowledge from soil science can be used to expand the understanding of IRES biogeochemistry. Based …

Synthesis, Characterisation And Dna Intercalation Studies Of Regioisomers Of Ruthenium (Ii) Polypyridyl Complexes, Laura Perdisatt, Samar Moqadasi, Luke O'Neill, Gary Hessman, Alessandra Ghion, Muhammad Qasim Mushtaq Warraich, Alan Casey, Christine O'Connor

Articles

Regioisomers of the functional group of the main ligand (L) on a series of [Ru(phen)2L]2+and [Ru(bpy)2L]2+ complexes, where phen is 1,10 phenanthroline and bpy is 2,2′-bipyridine, were synthesised to investigate the interaction with deoxyribonucleic acid (DNA) as potential therapeutics. UV–Vis binding titrations, thermal denaturation and circular dichroism were used to evaluate their interaction with DNA. The conclusions indicated the significance of the auxiliary ligand; especially 1,10-phenanthroline has on the binding constants (Kb). The systematic variation of auxiliary ligand(phen or bpy), and polypyridyl ligand (4-(1H-Imidazo[4,5-f][1,10]phenanthrolin-2-yl)benzonitrile (CPIP), 2-(4-formylphenyl)imidazo[4,5-f] [1,10] phenanthroline (FPIP), 2-(4-bromophenyl)imidazo[4,5-f][1,10]phenanthroline (BPIP) and 2-(4-nitrophenyl)imidazo[4,5-f] [1,10] phenanthroline (NPIP), split in terms of …

Vibrational Spectroscopic Analysis Of Body Fluids: Avoiding Molecular Contamination Using Centrifugal Filtration, Franck Bonnier, Matthew Baker, Hugh Byrne

Articles

The use of centrifugal filtration for protein purification and concentration represents an important improvement for the application of vibrational spectroscopy to analysis of bodily fluids based on protein fractions with specific molecular weight. Vibrational spectroscopic techniques are highly specific and can potentially detect small variations in the protein content indicating the presence of different diseases, therefore usable as markers for early diagnostic. However, due to the high sensitivity of the techniques, it is essential to verify that no molecular contamination occurs during the preparation of the samples. Concentration of the blood serum using commercially available centrifugal filters has been shown …

Raman Spectroscopic Analysis Of Human Skin Tissue Sections Ex-Vivo: Evaluation Of The Effects Of Tissue Processing And Dewaxing, Syed Mehmood Ali, Franck Bonnier, Ali Tfayli, Helen Lambkin, Kathleen Flynn, Vincent Mcdonagh, Claragh Healy, Thomas Lee, Fiona Lyng, Hugh Byrne

Articles

Raman spectroscopy coupled with K-means clustering analysis (KMCA) is employed to elucidate the biochemical structure of human skin tissue sections, and the effects of tissue processing. Both hand and thigh sections of human cadavers were analysed in their unprocessed and formalin fixed paraffin processed (FFPP) and subsequently dewaxed forms. In unprocessed sections, KMCA reveals clear differentiation of the stratum corneum, intermediate underlying epithelium and dermal layers for sections from both anatomical sites. The stratum corneum is seen to be relatively rich in lipidic content; the spectrum of the subjacent layers is strongly influenced by the presence of melanin, while that …