Atomic force microscopy study of peptides homologous to beta-domain of alpha-lactalbumins

Symmetrical peptide GYDTQAIVENNESTEYG (WT, Wild Type) identical to 35-51 aminoacid residues of human alpha-lactalbumin (HLA) and peptide GYDTQTVVNNNGHTDYG (ID, IDeal symmetry) homologous to beta-domain of mammalian alpha-lactalbumins can form amyloid-like fibrils in conditions required for fibrillogenesis of HLA. The latter peptide can also form fibrils in deionized water. Fibrils formed by these peptides can cause forming of HLA amyloid-like aggregates in physiological conditions. These results provide an evidence for presence of amyloidogenic determinant in beta-domain of alpha-lactalbumin. Thus, symmetry in the primary structure may play the role in fibrillogenesis of proteins.     

Ebola hemorrhagic fever: Properties of the pathogen and development of vaccines and chemotherapeutic agents

Molecular Biology - Ebola hemorrhagic fever (EHF) epidemic currently ongoing in West Africa is not the first among numerous epidemics in the continent. Yet it seems to be the worst EHF epidemic...     

Discordance in the distribution of markers of different inheritance systems (nDNA,mtDNA, and Chromosomes) in the superspecies complex <Emphasis Type="Italic">Mus musculus</Emphasis> as a result of extensive hybridization in primorye

The genetic structure of eight Mus musculus L. populations in Primorskii krai was studied with the use of taxon-specific markers of different inheritance systems: nDNA (RAPD), mtDNA (D-loop), and chromosomes. The results obtained demonstrate that although the compared nuclear marker characteristics (nDNA and chromosomes) have the same basis they are not linke with each other and, moreover, are often mutually inconsistent. Discordance in the inheritance of the marker characteristics in most of the animals studied is a result of extensive hybridization involving two to four house mouse subspecies. To identify taxonspecific nuclear markers revealed by RAPD, some RAPD PCR products were cloned, and their localization on chromosomes was determined. It was found that some fragments similar in size consist of two different comigrating sequences that are localized on different chromosomes and belong to different subspecies. All sequenced anonymous markers are localized in protein-coding genes. The functions of genes containing the marker sequences have been established. Differences in the taxon-specific RAPD fragments are associated with changes in the structure of important functional genes, and this can be considered as a significant genetic marker.     

Influence of phytosphingosine-type ceramides on the structure of DMPC membrane

The present paper describes the influence of the ceramides with phytosphingosine base, N-stearoylphytosphingosine (Cer[NP]) and alpha-hydroxy-N-stearoylphytosphingosine (Cer[AP]), on the structure and properties of multilamellar (MLVs) and unilamellar vesicles (ULVs) of dimyristoylphosphatidylcholine (DMPC). The lamellar repeat distance, D, has been measured at various temperatures using small angle X-ray diffraction. The incorporation of ceramides into the DMPC membrane causes larger D compared to pure DMPC membrane. For both ceramide types, at 32 degrees C, there is a linear relationship between the D value and the ceramide concentration. However, there is no such dependence at 13 or 60 degrees C. Unlike Cer[AP], Cer[NP] induces a new phase with a repeat distance of 38.5A. The membrane thickness and the vesicle radius of ULVs in water and in sucrose solution were calculated from small angle neutron scattering curves. Phytosphingosine ceramides increase both the membrane thickness and the radius in comparison to pure DMPC ULVs. The stability of ULVs in time was studied by dynamic light scattering. Both ceramides induce an aggregation of the ULVs into micrometer sized non-multilamellar structures in pure water. Presence of sucrose in the environment averts the vesicle aggregation.     

Molecular morphology of eukaryotic class I translation termination factor eRF1 in solution

The integral structural parameters and the shape of the molecule of human translation termination factor eRF1 were determined from the small-angle X-ray scattering in solution. The molecular shapes were found by bead modeling with nonlinear minimization of the root-mean-square deviation of the calculated from the experimental scattering curve. Comparisons of the small-angle scattering curves computed for atomic-resolution structures of eRF1 with the experimental data on scattering from solution testified that the crystal and the solution conformations are close. In the ribosome, the distance between the eRF1 motifs GGQ and NIKS must be shorter than in crystal or solution (75 versus 107-112 A). Therefore, like its bacterial counterpart RF2, the eukaryotic eRF1 must change its conformation as it binds to the ribosome. The conformational mobility of eukaryotic and prokaryotic class-1 release factors is another feature making them functionally akin to tRNA.     

Interaction of viral and cellular genes in cervical tumors

The results obtained in the Laboratory of Molecular Biology of Viruses, CRC carried out in the framework of the Human Genome program and devoted to the study of the activity of cell and viral genes in cervical cancer are summarized. DNA of human papillomaviruses persists in tumors both in episomal and integrative forms. Integration may occur in different regions of chromosomes. Viral transforming genes E6 and E7 are always present in tumor cells, while antibodies to these proteins are detected only in approximately 30% of patients. Loss of heterozygosity is detected on long and short arms of chromosome 6; some such cases are manifest already at the early stages of tumor progression, while others are typical of the late stages. Several genes that are potentially involved in tumorigenesis and are subject to hypermethylation in CpG islands were identified. Methylation of several genes is observed in approximately 30% of tumors. Tumor progression is associated with increased expression of p16ink4a, an inhibitor of cyclin-dependent kinases.     

Epizootics of "avian" influenza as the manifestation of pandemic

In this review of literature modern notions on the role of birds in the evolution of the pathogenicity signs and immune system of the main and intermediate hosts of influenza viruses, as well as on the mechanisms of overcoming interspecific barriers, are analyzed. The chronology of the spread of "avian" influenza among humans, starting from 1997, the properties of the natural reservoir of this infection, and in particular influenza viruses A, the ways of their variability and evolution are presented. The conclusion has been made that the mixing, joint evolution, recombination and reassortment of viral genomes may be caused by global events in individual geographical regions.     

What can we learn about the lipid vesicle structure from the small-angle neutron scattering experiment?

Small-angle neutron scattering (SANS) on the unilamellar vesicle (ULV) populations (diameter 500 and 1,000 Å) in D₂O was used to characterize lipid vesicles from dimyristoylphosphatidylcholine (DMPC) at three phases: gel L_β′, ripple P_β′ and liquid L_α. Parameters of vesicle populations and internal structure of the DMPC bilayer were characterized on the basis of the separated form factor (SFF) model. Vesicle shape changes from nearly spherical in the L_α phase to elliptical in the P_β′ and L_β′ phases. This is true for vesicles prepared via extrusion through pores with the diameter 500 Å. Parameters of the internal bilayer structure (thickness of the membrane and the hydrophobic core, hydration and the surface area of the lipid molecule) were determined on the basis of the hydrophobic–hydrophilic (HH) approximation of neutron scattering length density across the bilayer ρ(x) and of the step function (SF) approximation of ρ(x). DMPC membrane thickness in the L_α phase (T=30°C) demonstrates a dependence on the membrane curvature for extruded vesicles. Prepared via extrusion through 500 Å diameter pores, vesicle population in the L_α phase has the following characteristics: average value of minor semi-axis 266±2 Å, ellipse eccentricity 1.11±0.02, polydispersity 26%, thickness of the membrane 48.9±0.2 Å and of the hydrophobic core 19.9±0.4 Å, surface area 60.7±0.5 Ų and number of water molecules 12.8±0.3 per DMPC molecule. Vesicles prepared via extrusion through pores with the diameter 1,000 Å have polydispersity of 48% and membrane thickness of 45.5±0.6 Å in the L_α phase. SF approximation was used to describe the DMPC membrane structure in L_β′ (T=10°C) and P_β′ (T=20°C) phases. Extruded DMPC vesicles in D₂O have membrane thickness of 49.6±0.5 Å in the L_β′ phase and 48.3±0.6 Å in the P_β′ phase. The dependence of the DMPC membrane thickness on temperature was restored from the SANS experiment.     

Influence of external periodic stimuli on heart rate variability in healthy subjects and in coronary heart disease patients

Frequency estimates of the heart rate variability (HRV) spectrum influenced by external periodic stimuli were studied in healthy subjects and patients with coronary heart disease (CHD). Sensory stimulation by periodic eye opening at a rate of 15, 10, 8, 6, or 5 times per minute, as well as spontaneous and controlled breathing at a rate of 15, 10, 8, 6, or 5 times per minute, was used. It was found that the spectral response to external periodic oscillations was determined by a frequency-dependent phenomenon, the maximal amplitude of heart rate variations being observed in the case of external stimuli at a frequency of 0.1 Hz. A resonance frequency in the 0.1-Hz range may be suggested to exist in the cardiovascular controls. Significant differences in the HRV frequency characteristics between CHD patients and healthy subjects were shown. CHD patients had a characteristic decline in HRV responses to external oscillations; the power of these responses did not depend on the frequency of external stimuli.