Effect of self-association on the structural organization of partially folded proteins: inactivated actin

The propensity to associate or aggregate is one of the characteristic properties of many nonnative proteins. The aggregation of proteins is responsible for a number of human diseases and is a significant problem in biotechnology. Despite this, little is currently known about the effect of self-association on the structural properties and conformational stability of partially folded protein molecules. G-actin is shown to form equilibrium unfolding intermediate in the vicinity of 1.5 M guanidinium chloride (GdmCl). Refolding from the GdmCl unfolded state is terminated at the stage of formation of the same intermediate state. An analogous form, known as inactivated actin, can be obtained by heat treatment, or at moderate urea concentration, or by the release of Ca(2+). In all cases actin forms specific associates comprising partially folded protein molecules. The structural properties and conformational stability of inactivated actin were studied over a wide range of protein concentrations, and it was established that the process of self-association is rather specific. We have also shown that inactivated actin, being denatured, is characterized by a relatively rigid microenvironment of aromatic residues and exhibits a considerable limitation in the internal mobility of tryptophans. This means that specific self-association can play an important structure-forming role for the partially folded protein molecules.     

The sulfite molecule enhances homocysteine toxicity in SH-SY5Y cells

Molecular Biology Reports - Homocysteine (hcy) is an amino acid that contains sulfur species. In healthy individuals, plasma hcy levels are low. The aim of this study was to investigate the...     

Normal Autophagic Activity in Macrophages from Mice Lacking Gαi3, AGS3, or RGS19

In macrophages autophagy assists antigen presentation, affects cytokine release, and promotes intracellular pathogen elimination. In some cells autophagy is modulated by a signaling pathway that employs Gα_i3, Activator of G-protein Signaling-3 (AGS3/GPSM1), and Regulator of G-protein Signaling 19 (RGS19). As macrophages express each of these proteins, we tested their importance in regulating macrophage autophagy. We assessed LC3 processing and the formation of LC3 puncta in bone marrow derived macrophages prepared from wild type, Gnai3^-/-, Gpsm1^-/-, or Rgs19^-/- mice following amino acid starvation or Nigericin treatment. In addition, we evaluated rapamycin-induced autophagic proteolysis rates by long-lived protein degradation assays and anti-autophagic action after rapamycin induction in wild type, Gnai3^-/-, and Gpsm1^-/- macrophages. In similar assays we compared macrophages treated or not with pertussis toxin, an inhibitor of GPCR (G-protein couple receptor) triggered Gα_i nucleotide exchange. Despite previous findings, the level of basal autophagy, autophagic induction, autophagic flux, autophagic degradation and the anti-autophagic action in macrophages that lacked Gα_i3, AGS3, or RGS19; or had been treated with pertussis toxin, were similar to controls. These results indicate that while Gα_i signaling may impact autophagy in some cell types it does not in macrophages.     

Determination of Dynamical Heterogeneity from Dynamic Neutron Scattering of Proteins

Motional displacements of hydrogen (H) in proteins can be measured using incoherent neutron-scattering methods. These displacements can also be calculated numerically using data from molecular dynamics simulations. An enormous amount of data on the average mean-square motional displacement (MSD) of H as a function of protein temperature, hydration, and other conditions has been collected. H resides in a wide spectrum of sites in a protein. Some H are tightly bound to molecular chains, and the H motion is dictated by that of the chain. Other H are quite independent. As a result, there is a distribution of motions and MSDs of H within a protein that is denoted dynamical heterogeneity. The goal of this paper is to incorporate a distribution of MSDs into models of the H incoherent intermediate scattering function, $I\left(Q,t\right)$, that is calculated and observed. The aim is to contribute information on the distribution as well as on the average MSD from comparison of the models with simulations and experiment. For example, we find that simulations of $I\left(Q,t\right)$ in lysozyme are well reproduced if the distribution of MSDs is bimodal with two broad peaks rather than a single broad peak.     

Concentrations of copper, zinc and various elements in serum of patients with bronchial asthma.

In this study, serum copper, zinc, magnesium, iron and calcium concentrations were investigated in 40 patients with bronchial asthma (BA) and in 43 healthy subjects. Copper and calcium levels were found to be increased in patients with BA compared to the control group (p < 0.001 and p < 0.001 respectively). On the other hand, the serum zinc level was significantly lower in healthy subjects (p < 0.01). No changes were found in serum magnesium and iron levels in patients with BA compared to controls. In addition to various elements, certain serum proteins such as albumin, transferrin and ferritin were also assessed to determine whether there was a relationship between the elements and proteins in patients with BA. There was only a significant decrease in albumin concentration in patients with BA (p < 0.05).     

The influence of the sleep-wake cycle on primary monosymptomatic nocturnal enuresis: a non-randomized comparative study

Backround: Enuresis implies severe stress in affected children, and impairs quality of life and sleep. Children with enuresis experience difficulties in their arousal from sleep, possibly associated with disturbances of the circadian rhythm. In this study, we aimed to evaluate the sleep–wake cycle and sleep disturbances in children with monosymptomatic enuresis nocturna (MEN). Method: The study comprised 70 children with MEN who were admitted to the pediatrics and urology outpatients department and 94 age-matched healthy controls. Parents completed “Strengths and Difficulties Questionnaire,” Children’s Sleep Habits Questionnaire (CSHQ), Children’s Chronotype Questionnaire scale. Results: Children with enuresis had significantly more sleep and psychological problem. Enuresis group reported higher bedtime resistance, parasomnias, breathing-related problems, and daytime sleepiness in CHSQ (p < 0.05). Although circadian preference did not differ statistically between the groups (p > 0.05), sleep duration on school days and awakening and mid-sleep points, both on scheduled and free days, were found to be significantly different in the enuretic group (p < 0.05). In logistic regression analysis, age, sleep period on scheduled days, sleep inertia on scheduled and free days were significant predictor for enuresis. Discussion: Children with enuresis were more likely to experience problematic sleep. This may reflect that enuretic children have impaired sleep–wake cycles, leading to dysregulation of daily functional changes of bladder capacity and related hormones such as ADH. These findings might imply a sleep–wake disturbance in enuresis.