Molecular mechanisms of tumor angiogenesis

The maintenance of growth of malignant tumors is closely related with the development of the vascular network supplying the tumor with blood. The vascularization of tumor tissue is similar to physiological angiogenesis, but in tumors it has some specific features. During the last 25 years a vast number of biomolecules have been found and described which are involved in the regulation of tumor angiogenesis. This review considers the action mechanisms and specific features of expression of the main angiogenic growth factors, such as the vascular endothelium growth factor (VEGF), angiopoietins (Ang-1, Ang-2), and the basic fibroblast growth factor (bFGF). The roles of cytokines, growth factors, proteolytic enzymes, and cell adhesion molecules in the regulation of the key steps of blood vessel generation in the tumor are considered. The significance of angiogenesis in the treatment of oncological diseases and possible approaches for inhibition of the regulatory signals of angiogenic factors are discussed.     

Internal synchronization of the main 0.1-Hz rhythms in the autonomic control of the cardiovascular system

Synchronization parameters of 0.1-Hz rhythms isolated from the heart rate and the oscillations of the blood volume in microcirculatory vessels were studied in 12 healthy subjects and 32 patients with acute myocardial infarction. Recordings of the electrocardiogram and the pulsogram from the distal phalanx of the index finger, as well as mechanical recording of respiration with the body in a horizontal position, were performed. In patients with myocardial infarction, the recordings were performed during the first three to five days and the third week after the infarction. Synchronization was tested by plotting phase differences and calculating the total percentage of phase synchronization. Synchronization parameters of 0.1-Hz rhythms were high in healthy subjects. In patients with acute myocardial infarction, synchronization of 0.1-Hz rhythms was considerably poorer. The data obtained suggest that the studied 0.1-Hz rhythms are two independent oscillatory processes that are synchronized in healthy subjects. However, this interaction may be disturbed in cardiovascular pathologies, e.g., myocardial infarction.     

Functions of heat shock proteins in the system of adaptive immunity. Construction of vaccines

One of the most important aspects of heat shock proteins (HSP) functioning, namely their role in reactions of innate and adaptive immunity, was reviewed in the article. Mechanisms of involvement of HSP in processing and presentation of antigens to T-lymphocytes were described. Principles of construction of prophylactic and therapeutic vaccines on the basis of HSP were set out. Assessment of range of indications for their use and possible risks related with inductive action of vaccines on the development of immunopathologic processes was a specially discussed topic.     

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.     

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.