Comparison of the effects of UV-A radiation on Leptospira interrogan serovar Bataviae, Canicola and Pomona

Motivated by the lack of related studies and an insufficient understanding of the response of pathogenic spirochetes, including leptospira to ultraviolet-A (UV-A) (or other stresses), we comparatively studied the effects of UV-A radiation on the Leptospira interrogans serovar Bataviae,Canicola and Pomona. The main purpose of this work was to investigate the effects of UV-A irradiation—both short term (immediate) and long term (post-irradiation)—on leptospires at different UV-A dosages, controlled by the duration of exposure time. It was observed that survival fractionslinearly decrease from 100 to about 70, 60 and 50% for serovar Pomona, Bataviae and Canicola, respectively. This indicates that, for different serovars, UV-A irradiation has a quantitatively different effects on growth. Short term effects suggest that Pomona may be more resistant to UV-A than the other serovars. Long term effects show that, when compared with the control group, the treated groups of bacteria re-grow when the exposure time is equal or lesser than 6 h (~ 2 - 6), while the groupsexposed for 12 h or longer experienced little change or a slight decrease. This may indicate that UV-A radiation is able to inhibit the growth of bacteria, but does not prevent self-defense from taking place. UV-A radiation’s effect on antigenic components was also investigated. The immunoblotting method was used and the results are supported by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results. Possible explanations for these results are discussed

Improving Internal Peptide Dynamics in the Coarse-Grained MARTINI Model: Toward Large-Scale Simulations of Amyloid- and Elastin-like Peptides

We present an extension of the coarse-grained MARTINI model for proteins and apply this extension to amyloid- and elastin-like peptides. Atomistic simulations of tetrapeptides, octapeptides, and longer peptides in solution are used as a reference to parametrize a set of pseudodihedral potentials that describe the internal flexibility of MARTINI peptides. We assess the performance of the resulting model in reproducing various structural properties computed from atomistic trajectories of peptides in water. The addition of new dihedral angle potentials improves agreement with the contact maps computed from atomistic simulations significantly. We also address the question of which parameters derived from atomistic trajectories are transferable between different lengths of peptides. The modified coarse-grained model shows reasonable transferability of parameters for the amyloid- and elastin-like peptides. In addition, the improved coarse-grained model is also applied to investigate the self-assembly of β-sheet forming peptides on the microsecond time scale. The octapeptides SNNFGAIL and (GV)4 are used to examine peptide aggregation in different environments, in water, and at the water–octane interface. At the interface, peptide adsorption occurs rapidly, and peptides spontaneously aggregate in favor of stretched conformers resembling β-strands

Lipid (per) oxidation in mitochondria:an emerging target in the ageing process?

Lipids are essential for physiological processes such as maintaining membrane integrity, providing a source of energy and acting as signalling molecules to control processes including cell proliferation, metabolism, inflammation and apoptosis. Disruption of lipid homeostasis can promote pathological changes that contribute towards biological ageing and age-related diseases. Several age-related diseases have been associated with altered lipid metabolism and an elevation in highly damaging lipid peroxidation products; the latter has been ascribed, at least in part, to mitochondrial dysfunction and elevated ROS formation. In addition, senescent cells, which are known to contribute significantly to age-related pathologies, are also associated with impaired mitochondrial function and changes in lipid metabolism. Therapeutic targeting of dysfunctional mitochondrial and pathological lipid metabolism is an emerging strategy for alleviating their negative impact during ageing and the progression to age-related diseases. Such therapies could include the use of drugs that prevent mitochondrial uncoupling, inhibit inflammatory lipid synthesis, modulate lipid transport or storage, reduce mitochondrial oxidative stress and eliminate senescent cells from tissues. In this review, we provide an overview of lipid structure and function, with emphasis on mitochondrial lipids and their potential for therapeutic targeting during ageing and age-related disease

Alpha-tocopherol inhibits pore formation in oxidized bilayers

In biological membranes, alpha-tocopherols (α-toc; vitamin E) protect polyunsaturated lipids from free radicals. Although the interactions of α-toc with non-oxidized lipid bilayers have been studied, their effects on oxidized bilayers remain unknown. In this study, atomistic molecular dynamics (MD) simulations of oxidized lipid bilayers were performed with varying concentrations of α-toc. Bilayers with 1-palmitoyl-2-lauroyl-sn-glycero-3-phosphocholine (PLPC) lipids and their aldehyde derivatives at a 1 : 1 ratio were studied. Our simulations show that oxidized lipids self-assemble into aggregates with a water pore rapidly developing across the bilayer. The free energy of transporting an α-toc molecule in a bilayer suggests that α-tocs can passively adsorb into it. When α-toc molecules were present at low concentrations in bilayers containing oxidized lipids, water pore formation was slowed down. At high α-toc concentrations, no pores were observed. Based on the simulations, we propose that the mechanism of how α-toc inhibits pore formation in bilayers with oxidized lipids is the following: α-tocs trap the polar groups of the oxidized lipids at the membrane-water interface resulting in a decreased probability of the oxidized lipids making contact with the two leaflets and initiating pore formation. This demonstrates that α-toc molecules not only protect the bilayer from oxidation but also help to stabilize the bilayer after lipid peroxidation occurs. These results will help in designing more efficient molecules to protect membranes from oxidative stress

The hydrophobic effect and its role in cold denaturation

The hydrophobic effect is considered the main driving force for protein folding and plays an important role in the stability of those biomolecules. Cold denaturation, where the native state of the protein loses its stability upon cooling, is also attributed to this effect. It is therefore not surprising that a lot of effort has been spent in understanding this phenomenon. Despite these efforts, many unresolved fundamental aspects remain. In this paper we review and summarize the thermodynamics of proteins, the hydrophobic effect and cold denaturation. We start by accounting for these phenomena macroscopically then move to their atomic-level description. We hope this review will help the reader gain insights into the role played by the hydrophobic effect in cold denaturation. Keywords: Hydrophobic effect; Thermodynamics; Clathrate cages; Hydrate cages; Cold denaturation; Protein

The hydrophobic effect and its role in cold denaturation

The hydrophobic effect is considered the main driving force for protein folding and plays an important role in the stability of those biomolecules. Cold denaturation, where the native state of the protein loses its stability upon cooling, is also attributed to this effect. It is therefore not surprising that a lot of effort has been spent in understanding this phenomenon. Despite these efforts, many unresolved fundamental aspects remain. In this paper we review and summarize the thermodynamics of proteins, the hydrophobic effect and cold denaturation. We start by accounting for these phenomena macroscopically then move to their atomic-level description. We hope this review will help the reader gain insights into the role played by the hydrophobic effect in cold denaturation. Keywords: Hydrophobic effect; Thermodynamics; Clathrate cages; Hydrate cages; Cold denaturation; Protein