Aggregation of Aβ40/42 chains in the presence of cyclic neuropeptides investigated by molecular dynamics simulations

Alzheimer’s disease is associated with the formation of toxic aggregates of amyloid beta (Aβ) peptides. Despite tremendous efforts, our understanding of the molecular mechanisms of aggregation, as well as cofactors that might influence it, remains incomplete. The small cyclic neuropeptide somatostatin-14 (SST₁₄) was recently found to be the most selectively enriched protein in human frontal lobe extracts that binds Aβ₄₂ aggregates. Furthermore, SST₁₄’s presence was also found to promote the formation of toxic Aβ₄₂ oligomers in vitro. In order to elucidate how SST₁₄ influences the onset of Aβ oligomerization, we performed all-atom molecular dynamics simulations of model mixtures of Aβ₄₂ or Aβ₄₀ peptides with SST₁₄ molecules and analyzed the structure and dynamics of early-stage aggregates. For comparison we also analyzed the aggregation of Aβ₄₂ in the presence of arginine vasopressin (AVP), a different cyclic neuropeptide. We observed the formation of self-assembled aggregates containing the Aβ chains and small cyclic peptides in all mixtures of Aβ₄₂–SST₁₄, Aβ₄₂–AVP, and Aβ₄₀–SST₁₄. The Aβ₄₂–SST₁₄ mixtures were found to develop compact, dynamically stable, but small aggregates with the highest exposure of hydrophobic residues to the solvent. Differences in the morphology and dynamics of aggregates that comprise SST₁₄ or AVP appear to reflect distinct (1) regions of the Aβ chains they interact with; (2) propensities to engage in hydrogen bonds with Aβ peptides; and (3) solvent exposures of hydrophilic and hydrophobic groups. The presence of SST₁₄ was found to impede aggregation in the Aβ₄₂–SST₁₄ system despite a high hydrophobicity, producing a stronger “sticky surface” effect in the aggregates at the onset of Aβ₄₂–SST₁₄ oligomerization.     

Concentrations of myosin-activating protein kinases in the myocardium of patients with dilated cardiomyopathy and in animal heart

Skeletal myosin light chain kinase in the myocardia of various animal species was identified by immunoblotting. The myocardial concentrations of this protein and myosin-activating protein kinases (RhoA-activated kinase, integrin-linked kinase, and zipper-interacting kinase) were compared in healthy humans and patients with dilated cardiomyopathy. Skeletal myosin light chain kinase was detected in the human and chicken embryo hearts, rather than in the embryonic and adult rat hearts. In the myocardium of patients with dilated cardiomyopathy, the concentrations of myosin light chain kinase, RhoA-activated kinase, and integrin-linked kinase increase and the concentration of zipper-interacting kinase decreases. The results obtained are likely to characterize compensatory processes in cardiomyocytes in dilated cardiomyopathy that are aimed at increasing their viability and contractility.     

Incubation in uni-parental Arctic breeding waders

Bruinzeel, L., Tulp, I., Jukema, J. & Stepanova, O. 2000. Incubation in mi-parental arctic breeding waders. Ostrich 71 (1 & 2): 345.

Little Stints Calidris minuta are amongst the smallest breeding waders. This, in combination with the fact that they have a peculiar breeding system, in which each adult takes care of her/his own nest and young, puts high demands during incubation. Due to uni-parental feeding system, feeding time is limited. The accumulation of he1 stores prior to breeding may be crucial to get through the 21-day incubation period. Incubation rhythms, body mass dynamics and energy expenditure of Little Stints was studied at Medusa Bay, Western Taimyr in the summer of 1996. Repeated body mass measurements during incubation were taken by catching the birds on the nest. Concurrently, we measured nest attentiveness, using Tiny Talk dataloggers and temperature sensitive probes, which were placed in the nests. Arthropod availability was measured to estimate food availability. In comparison, body mass dynamics were also studied in Curlew Sandpiper, another uni-parental breeder, but three times bigger. The first (preliminary) results of this study were presented.     

Results of the comparative use of virological and bacteriological control of routine disinfection in maternity homes

Bacterial viruses were often detected in washings from different environmental objects; not infrequently, the inoculation of washings from the same objects resulted in the growth of Escherichia coli. The expediency of making parallel tests of washings from these objects for the presence of wild strains of bacterial and viral cultures both during the control of disinfection measures and the determination of the effectiveness of disinfection agents is shown.     

Strains of salmonella with altered antigenic structure]

The authors studied 260 freshly isolated and laboratory cultures of salmonellae belonging to different serological groups. Heterogeneity of the majority of the strains studied by colour fluorescence of the colonies in the oblique light flux was demonstrated. Genetically bound spontaneous stable mutants with a different antigenic composition were selected by this method from a number of serological types. The isolated mutants were in the S-form and failed to differ by morphological, cultural and biochemical properties from the initial parental strains. A study of the antigenic structure by the method of agar immunoelectrophoresis and determination of their serological properties showed the mutants to have disturbances in the processes of O- or K-antigen synthesis.     

Serological method of detecting the antigens of the causative agent of Sonne dysentery in lysates of the fecal inoculates from patients]

Serological method of detection of Sh. sonnei antigens in the lysates of the patients, fecal cultures is suggested and approved. In the majority of cases of the results of bacteriological and serological methods of study of the feces coincided. Data confirming the specificity of the antibody neutralization test (ANT) in Sonne dysentery are presented. In connection with detection of the screening action of the Vi-antigen of typhoid bacilli there were elaborated additional methods for verifying the specificity of the ANT results. It is recommended to keep agar plates after selection of suspicious colonies during the bacteriological test; the lysate of the microbial crop should be additionally subjected to the ANT, this considerably increasing the percentage of laboratory confirmations of dysentery caused by Sh. sonnei.     

Preparation and characterization of bioactive products obtained via the solubilization of brown coal by white rot fungi

We investigated the solubilizing activity of the Basidiomycete fungi Trametes hirsuta and Trametes maxima, with respect to brown coal (lignite) during liquid phase cultivation. We found that the degrading capacity of the fungi is determined by the activity of the ligninolytic enzymes Mn peroxidase and lignin peroxidase. We assessed the growth-stimulating activity of biopreparations (BPs), based on the culture liquids (CL) of the studied fungal strains, which were grown on a rich or minimal medium. We found that the obtained BPs inhibited the growth of wheat shoots and roots at the germination stage, but they either had no effect at later stages of plant growth or showed a mild stimulation. When basidiomycetes were cultivated in the presence of brown coal, the obtained BPs stimulated root growth at the germination stage, and did not influence plant growth (Trametes hirsuta) or stimulated it (Trametes maxima) at later stages. Further, we report a pronounced detoxifying ability of the BPs in respect to the atrazine herbicide. We suggest that this effect is caused by the laccases action, that are present in the studied BPs.