Universality in the timescales of internal loop formation in unfolded proteins and single-stranded oligonucleotides

Understanding the rate at which various parts of a molecular chain come together to facilitate the folding of a biopolymer (e.g., a protein or RNA) into its functional form remains an elusive goal. Here we use experiments, simulations, and theory to study the kinetics of internal loop closure in disordered biopolymers such as single-stranded oligonucleotides and unfolded proteins. We present theoretical arguments and computer simulation data to show that the relationship between the timescale of internal loop formation and the positions of the monomers enclosing the loop can be recast in a form of a universal master dependence. We also perform experimental measurements of the loop closure times of single-stranded oligonucleotides and show that both these and previously reported internal loop closure kinetics of unfolded proteins are well described by this theoretically predicted dependence. Finally, we propose that experimental deviations from the master dependence can then be used as a sensitive probe of dynamical and structural order in unfolded proteins and other biopolymers.     

Retinotopic organization of the lateral suprasylvian sulcus' posterior-medial area as revealed by analysis of the pattern of cortico-cortical connection with the cat 17th area

Using cortico-cortical connection analysis technique, the cat visual area PMLS (the area located on posterior medial wall of the lateral suprasylvian sulcus) retinotopic organization was investigated. A retrograde axonal tracer: horseradish peroxidase (HRP), was injected in the PMLS, and initial neurons were investigated in area 17. It was shown that after HRP injection in PMLS locus, where a central vision field is located, a labelled cell pattern in area 17 corresponded to the L. Palmer et al., 1978, retinotopic map. On the contrary, after HRP injection in PMLS locus, where an upper vision field must be located, as L. Palmer et al., 1978 predicted, initial neurons are visualized in area 17 loci where low visual periphery is displayed: -10 degrees to -60 degrees in vertical meridian and 40 degrees to 80 degrees in horizontal meridian. Such discrepancy in upper and lower visual field representation was also obtained in electrophysiological and topographic investigations by Grant, Shipp, 1991. The data suggest necessity of S. Grant and S. Shipp's retinotopic map use in the cat area PMLS morphofunctional investigation.     

FTIR and UV spectroscopy in real-time monitoring of S. cerevisiae cell culture

A combination of FTIR and UV spectroscopy is proposed as a novel technique for integrated real-time monitoring of metabolic activity and growth rates of cell cultures, required for systematic studies of cellular low-frequency (LF) electric and magnetic field (EMF) effects. As an example, we investigated simultaneous influence of periodic LF 3D EMFs on a culture of Saccharomyces cerevisiae (baker's yeast) cells. Amplitudes, frequencies and phases of the field components were the variable parameters. Electromagnetic fields were found to efficiently control the activity of the yeast cells, with the resulting CO(2) production rates, as monitored by FTIR spectroscopy, varying by at least one order of magnitude due to the field action. Additionally, population dynamics of the yeast cells was monitored by UV absorption of the yeast culture at λ(prob)?=?320?nm, and compared to the CO(2) production rates. The detected physiologically active frequencies are all below 1?kHz, namely, 800?Hz excitation was effective in reducing the metabolic rates and arresting cell proliferation, whereas 200?Hz excitation was active in accelerating both cell proliferation and overall metabolic rates. The proposed methods produce objective, reliable and quantitative real-time results within minutes and may be used in various tasks that could benefit from a rapid feedback they provide in the form of metabolic and growth rates. Amplitude and frequency dependences of the LF EMF effects from individual field components with different polarizations were recorded and qualitatively interpreted based on a simple model, describing ion diffusion through a membrane channel.     

Using demographic data to better interpret pitfall trap catches

The results of pitfall trapping are often interpreted as abundance in a particular habitat. At the same time, there are numerous cases of almost unrealistically high catches of ground beetles in seemingly unsuitable sites. The correlation of catches by pitfall trapping with the true distribution and abundance of Carabidae needs corroboration. During a full year survey in 2006/07 in the Lake Elton region (Volgograd Area, Russia), 175 species of ground beetles were trapped. Considering the differences in demographic structure of the local populations, and not their abundances, three groups of species were recognized: residents, migrants and sporadic. In residents, the demographic structure of local populations is complete, and their habitats can be considered "residential". In migrants and sporadic species, the demographic structure of the local populations is incomplete, and their habitats can be considered "transit". Residents interact both with their prey and with each other in a particular habitat. Sporadic species are hardly important to a carabid community because of their low abundances. The contribution of migrants to the structure of carabid communities is not apparent and requires additional research. Migrants and sporadic species represent a "labile" component in ground beetles communities, as opposed to a "stable" component, represented by residents. The variability of the labile component substantially limits our interpretation of species diversity in carabid communities. Thus, the criteria for determining the most abundant, or dominant species inevitably vary because the abundance of migrants in some cases can be one order of magnitude higher than that of residents. The results of pitfall trapping adequately reflect the state of carabid communities only in zonal habitats, while azonal and disturbed habitats are merely transit ones for many species of ground beetles. A study of the demographic structure of local populations and assessment of the migratory/residential status of particular carabid species are potential ways of increasing the reliability of pitfall trap information.     

Synthesis of modified peptides with C-terminal alpha-amino aldehydes]

Various synthetic approaches to modified peptides with the C-terminal aldehyde group, capable of inhibiting a number of proteolytic enzymes belonging to the classes of thiol, serine, and aspartyl proteases, are considered. Both chemical methods, including solid phase peptide synthesis now widely used, and biocatalytic synthetic methods for obtaining these substances are discussed in detail.     

Highly pathogenic avian influenza virus inducing influenza pneumonia in humans

The human disease caused by avian influenza virus in South Asia is a typical example of emerging infection resulting from transmission of a known causative agent to a new host. The first cases with a comparatively high level of lethality rates among patients were registered in 1997 and 1999. The situation is a special phenomenon in epidemiology which requires deep evolutionary and ecological analysis, as well as theoretical interpretation. With the example of avian influenza virus in Western Europe and South Asia in 2003-2004 the practical expediency of modern concepts "foci versus epidemics" and "eradication versus vaccination" is now evident.     

Why ribonucleases cause death of cancer cells

Molecular properties and possible mechanisms of action of cytotoxic ribonucleases (RNases), potential antitumor therapeutics, are characterized. The analysis of recent publications and own experimental results have allowed the authors, on the one hand, to distinguish cellular components that are responsible for selective activity of exogenous RNases towards malignant cells, and on the other--to identify the contribution of definite molecular determinants to the enzyme cytotoxicity. The predominant effect of the RNase molecule charge on the cell death induction is shown. The RNase cytotoxic effects are caused by catalytic cleavage of available RNA, by products of its hydrolysis, as well as by non-catalytic electrostatic interaction of exogenous enzyme with cell components. Potential targets for RNase action in a cancer cell have been revealed. The role of modulation of the membrane calcium-dependent potassium channels and ras-oncogene functions in the RNase-induced cell damage is defined. The effect of cytotoxic RNases on gene expression via influencing the RNA interference is discussed.     

Orbitrap mass analyzer--overview and applications in proteomics

The orbitrap mass analyzer is proving itself as a useful addition to a proteomics tool box. The key attributes of this analyzer are accurate mass and high resolution similar to those achievable with FT ICR instrumentation. The basic principles underlying these capabilities, and how they translate into benefits in real-life proteomics experiments are discussed. The focus is on reviewing examples of protein identification with bottom-up and top-down approaches, and detection of post-translational modifications.