Biology subjects

Whitten, D.

Publications and source records attributed to Whitten, D..

3 recordsLinked to original sources

bioRxiv2021

Controlled and Selective Photo-oxidation of Amyloid-β Fibrils by Oligomeric p-Phenylene Ethynylenes

Photodynamic therapy (PDT) has been explored as a therapeutic strategy to clear toxic amyloid aggregates involved in neurodegenerative disorders such as Alzheimers disease. A major limitation of PDT is off-target oxidation, which can be lethal for the surrounding cells. We have shown that a novel class of oligo-p-phenylene ethynylene-based compounds (OPEs) exhibit selective binding and fluorescence turn-on in the presence of pre-fibrillar and fibrillar aggregates of disease-relevant proteins such as amyloid-{beta} (A{beta}) and -synuclein. Concomitant with fluorescence turn-on, OPE also photosensitizes singlet oxygen under illumination through the generation of a triplet state, pointing to the potential application of OPEs as photosensitizers in PDT. Herein, we investigated the photosensitizing activity of an anionic OPE for the photo-oxidation of toxic A{beta} aggregates and compared its efficacy to the well-known but non-selective photosensitizer methylene blue (MB). Our results show that while MB photo-oxidized both monomeric and fibrillar conformers of A{beta}40, OPE oxidized only A{beta}40 fibrils, targeting two histidine residues on the fibril surface and a methionine residue located in the fibril core. Oxidized fibrils were shorter and more dispersed, but retained the characteristic {beta}-sheet rich fibrillar structure and the ability to seed further fibril growth. Importantly, the oxidized fibrils displayed low toxicity. We have thus discovered a class of novel theranostics for the simultaneous detection and oxidization of amyloid aggregates. Importantly, the selectivity of OPEs photosensitizing activity overcomes the limitation of off-target oxidation of currently available photosensitizers, and represents a significant advancement of PDT as a viable strategy to treat neurodegenerative disorders.

neuroscience↗

bioRxiv2021

Rapid and Effective Inactivation of SARS-CoV-2 by a Cationic Conjugated Oligomer with Visible Light: Studies of Antiviral Activity in Solutions and on Supports

This paper presents results of a study of a new cationic oligomer that contains end groups and a chromophore affording inactivation of SARS-Cov-2 by visible light irradiation in solution or as a solid coating on wipes paper and glass fiber filtration substrates. A key finding of this study is that the cationic oligomer with a central thiophene ring and imidazolium charged groups give outstanding performance in both killing of E. coli bacterial cells and inactivation of the virus at very short times. Our introduction of cationic N-Methyl Imidazolium groups enhances the light-activation process for both E. coli and SARS-Cov-2 but dampens the dark killing of the bacteria and eliminates the dark inactivation of the virus. For the studies with this oligomer in solution at concentration of 1 g/mL and E. coli we obtain 3 log killing of the bacteria with 10 min irradiation with LuzChem cool white lights (mimicking indoor illumination). With the oligomer in solution at a concentration of 10 g/mL, we observe 4 logs inactivation (99.99 %) in 5 minutes of irradiation and total inactivation after 10 min. The oligomer is quite active against E. coli on oligomer-coated wipes papers and glass fiber filter supports. The SARS-Cov-2 is also inactivated by the oligomer coated glass fiber filter papers. This study indicates that these oligomer-coated materials may be very useful as wipes and filtration materials.

biochemistry↗

bioRxiv2020

Unique Proteomes Implicate Functional Specialization across Heterocysts, Akinetes, and Vegetative Cells in Anabaena cylindrica

In response to environmental changes, vegetative cells of Anabaena cylindrica can differentiate into two other cell types: a heterocyst for oxic N2-fixation, and an enlarged spore called akinete for stress survival. Akinetes normally differentiate from vegetative cells adjacent to heterocysts. Heterocysts inhibit nearby cells from differentiating into heterocysts but can induce adjacent cells to become akinetes, a rare embryogenetic induction in prokaryotes. The mechanism for a patterned differentiation in A. cylindrica has been little studied. Here, we isolated three types of cells from A. cylindrica to identify their proteomes using LC-MS/MS. A total of 1395 proteins were identified, including 664 proteins from akinetes, 751 proteins from heterocysts, and 1236 proteins from vegetative cells. There were 45 proteins (33 novel proteins) found exclusive to akinetes, 57 heterocyst-specific proteins (33 novel proteins), including nif gene products, and 485 proteins exclusively in vegetative cells. Our proteomic data suggest that akinetes, unlike the typical spores of bacteria, perform unique biochemical functions that collaborate with both heterocysts and vegetative cells. A HAVe model for collaboration among heterocysts, akinetes and vegetative cells is proposed to illustrate the metabolic network of cyanophycin and carbohydrates based on the distribution of their biosynthesis related proteins in three types of cells. Interestingly, cell division proteins, DNA replication proteins, some carboxysomal proteins including RuBisCO and proteins in photosystems I, II were found abundant in heterocysts, the non-dividing cells dedicated exclusively to oxic N2-fixation. The identification of the akinete and heterocyst proteomes enables the pursuit of genetic studies into the patterned differentiation of akinetes and heterocysts.

microbiology↗