Biology subjects

Otzen, D. E.

Publications and source records attributed to Otzen, D. E..

21 records · Page 2Linked to original sources

bioRxiv2020

Overexpression of human alpha-synuclein leads to dysregulated microbiome and metabolites with ageing in a rat model of Parkinson disease

Since Braaks hypothesis stating that sporadic Parkinsons disease follows a specific progression of the pathology from the peripheral to the central nervous system and can be monitored by detecting accumulation of the alpha-Synuclein protein. There is growing interest in understanding how the gut (commensal) microbiome can regulate alpha-Synuclein accumulation which can lead to PD. We studied a transgenic rat model overexpressing the human alpha-Synuclein and found that the protein overexpression resulted in gut alpha-Synuclein expression and aggregation in the gut neurons with advancing age. A progressive gut microbial composition alteration characterized by the reduction of Firmicutes to Bacteroidetes ratio could be detected in the young transgenic rat model and interestingly this ratio was then increased with aging. This observation was accompanied in older animals by intestinal inflammation, increase gut permeability and a robust alteration in metabolites production characterized by the increase of succinate level in the feces and serum. Manipulation of the gut bacteria by short-term antibiotics treatment revealed a complete loss of short-chain fatty acids (SCFAs) and reduction in succinate levels. Although antibiotics treatment did not change alpha-synuclein expression in the enteric nervous system of the colon, it can reduce alpha-synuclein expression in the olfactory bulb of the transgenic rats. In summary, synchronous with ageing, our data emphasize that the gut microbiome dysbiosis leads to a specific alteration of gut metabolites which are reflected in the serum and can be modulated by the environment.

neuroscience↗

bioRxiv2020

Adsorption of Azo Dyes by a Novel Bio-Nanocomposite Based on Whey Protein Nanofibrils and Montmorillonite: Equilibrium Isotherm and Kinetic Modeling

Excessive discharge of hazardous azo dyes into the aquatic ecosystem is a global environmental concern. Here, we develop a green approach to remediate dye pollutions in water by fabricating an easy-separable bio-nanocomposite, based on whey protein concentrate, its nanofibrils, and montmorillonite nano-clay. To characterize the nanocomposite, we used SEM, FT-IR, XRD, and BET techniques. Nanofibrils lead to a uniform dispersion of montmorillonite in the whey protein matrix and also reinforce the nanocomposite. The adsorption efficacy was monitored in a batch system, using cationic dyes (Chrysoidine-G, Bismarck brown-R), reactive dyes (reactive black-5, reactive orange-16), acid dyes (acid red-88, acid red-114), and direct dyes (direct violet-51, Congo red). This nanocomposite adsorbed different dye classes, cationic dyes quicker (> 82%, after 4 h), and reactive dyes slower. Then, the effect of initial dye concentration, pH, contact time, adsorbent dose, and temperature on Chrysoidine-G adsorption was explored. The adsorbent showed a high removal (>93%) for a wide concentration range of Chrysoidine-G, also acidic pH and higher temperature are more favorable for the process. Equilibrium adsorption parameters were reasonably fitted with a linear (Nernst) isotherm model. The results indicated the existence of an unlimited number of absorption sites, i.e. no saturation was achieved under our experimental conditions (qmax(Exp)= 731 mg/g). Kinetic data were fitted with pseudo-second-order and intra-particle diffusion models. We conclude that this nanocomposite is a green adsorbent with potential use for wastewater treatment and related purposes. HighlightsO_LIWe produced an easy-separable bio-nanocomposite using whey nanofibrils and MMT, with high adsorption capacity C_LIO_LINanofibrils help disperse MMT particles uniformly in the WP matrix C_LIO_LIThe adsorbents performance was compared to the adsorbents in absence of MMT and nanofibrils C_LIO_LIThis composite adsorbs cationic, anionic, direct and reactive azo dyes with different kinetics C_LIO_LIAdsorption isotherms and kinetics are studied in detail C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=82 SRC="FIGDIR/small/394205v3_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@13aa68eorg.highwire.dtl.DTLVardef@18cc8c0org.highwire.dtl.DTLVardef@1cff49eorg.highwire.dtl.DTLVardef@1c4de1c_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2020

Quantitating denaturation by formic acid: Imperfect repeats are essential to the stability of the functional amyloid protein FapC

Bacterial functional amyloids are evolutionarily optimized to aggregate to help them fulfil their biological functions, e.g. to provide mechanical stability to biofilm. Amyloid is formed in Pseudomonas sp. by the protein FapC which contains 3 imperfect repeats connected by long linkers. Stepwise removal of these repeats slows down aggregation and increases the propensity of amyloids to fragment during the fibrillation process, but how these mechanistic properties link to fibril stability is unclear. Here we address this question. The extreme robustness of functional amyloid makes them resistant to conventional chemical denaturants, but they dissolve in formic acid (FA) at high concentrations. To quantify this, we first measured the denaturing potency of FA using 3 small acid-resistant proteins (S6, lysozyme and ubiquitin). This revealed a linear relationship between [FA] and the free energy of unfolding with a slope of mFA, as well as a robust correlation between protein residue size and mFA. We then measured the solubilisation of fibrils formed from different FapC variants (with varying number of repeats) as a function of [FA]. The resulting mFA values revealed a decline in the number of residues driving amyloid formation when at least 2 repeats were deleted. The midpoint of denaturation declined monotonically with progressive removal of repeats and correlated with solubility in SDS. Complete removal of all repeats led to fibrils which were solubilized at FA concentrations 2-3 orders of magnitude lower than the repeat-containing variants, showing that at least one imperfect repeat is required for the stability of functional amyloid.

biophysics↗