Biophysics最新文献

The aim of this study was to develop an experimental and theoretical method for determining the speed of sound in the lung parenchyma. The method is based on measuring the impedance characteristics of the Helmholtz resonator; the studied lungs were placed in its cavity. The input impedance of the Helmholtz resonator corresponds to a parallel connection of the impedance of the lungs and a separate resonator. A modified two-microphone method was used to measure the resonant frequency and the input impedance characteristic of the resonator with lungs. The installation consisted of a loudspeaker, a waveguide, two measuring microphones, and an impedance termination with a tube for connecting a Helmholtz resonator with specified geometric characteristics. When the lungs were inserted into the volume of the Helmholtz resonator, the frequency did not increase in proportion to the decrease in volume, which indicated an abnormally low speed of sound in the lung parenchyma. The difference between the calculated and measured resonant frequencies was used to determine the speed of sound in the lung parenchyma. Measurements were carried out on the inflated and collapsed lungs of eight conditionally healthy rabbits. Two variants of sound transmission in the lung parenchyma corresponding to isothermal and adiabatic processes were considered. The results of measurements and calculations indicated that the speed of sound in the lung parenchyma of a conditionally healthy rabbit is 21–22 m/s, which corresponds to modern theoretical concepts.

The wind speed, the sea surface temperature, the chlorophyll a concentration (MODIS-Aqua/Terra satellite data), the bioluminescence intensity and biomass of zooplankton (data collected onboard a research vessel), the primary productivity, and the indices of lower-than-normal atmospheric pressure and water mass transfer (model calculations) were used to assess the current state and functional characteristics of a pelagic ecosystem of the northern open areas of the Black Sea. The ecosystem was found to have reached a state of relative stability in its structure and function in the past two decades (2000–2020), after natural cataclysms associated with eutrophication and trophic pressure from invasive plankton species in the 1990s. The state is characterized by the absence of trends in the interannual variability of its identifying parameters. The problem of regional differences in long-term trends of physical factors and biological interactions is discussed on a broader (global) scale.

Understanding physical chemistry underlying drug-protein interaction is essential to devise guidelines for the synthesis of target-oriented drugs. In the present study, the effects of the non-steroidal anti-inflammatory drug (NSAID), diclofenac sodium (DCF) on the stability and structure of Bovine Pancreatic Ribonuclease-A (RNase-A) taken as model protein has been examined by thermal stability, circular dichroism, intrinsic fluorescence, and docking studies. Since drug-protein interaction is an important pharmacokinetic parameter of a drug, it was deemed significant to study the effects of DCF on protein structure and stability. When the thermodynamic parameters were assessed, DCF was observed to destabilized RNase-A in terms of T_m and (Delta G_{{text{D}}}^{^circ }) while the addition of osmolytes stabilized the protein. In the presence of DCF and osmolyte, a change in the tertiary structure but not in the secondary structure of the protein was observed. The fluorescence study showed a decrease in the fluorescence intensity confirming the quenching of RNase-A fluorescence by DCF and osmolytes. Molecular docking studies revealed the involvement of hydrogen bonds and Van der Waals in RNase-A-DCF interaction. The activity of this enzyme RNAse-A is decreased in presence of DCF while osmolyte helps bring back the activity by increasing k_cat and decreasing K_m values. This study will provide the platform for the use of combinatorial therapy of DCF with osmolytes to offsets the harmful effects of DCF.

Methods of automatic feature extraction attract increasing attention when solving modern image processing problems. Confocal images of the single-layer epithelium of the developing eye of the fruit fly drosophila are a convenient model system for the development of methods for the identification of complex features. The aim of this study was to use Cartesian genetic programming to identify the boundaries of ommatidia, the photosensitive units of the developing eye. The use of Cartesian genetic programming to analyze the expression patterns of the Fasciclin III marker showed good results. This provides interesting prospects for further application of this technology for the automatic analysis of images obtained using confocal microscopy.

It has been shown that the release of half of nitrosyl ligands from iron-dinitrosyl fragments in binuclear dinitrosyl iron complexes with thiol-containing ligands in the form of nitrosonium (NO⁺) cations during the decay of these complexes in acidic solutions increased with a decrease in the stability of these complexes and completely stopped with an increase in the concentration of free thiols (not included in binuclear dinitrosyl iron complexes) to the level exceeding the concentration of iron-dinitrosyl fragments by two or more times. The first factor manifested itself in the fact that less stable complexes with mercaptosuccinate decomposed in an acidic medium at room temperature, whereas the decay of more stable complexes with glutathione occurred only when their solutions were heated at 80°C. The cessation of the release of NO⁺ cations from complexes with an increase in the level of free thiols in solution was determined by the ability of the latter to initiate the reduction of NO⁺ cations to NO.

Alu elements constitute a notable part of the human genome and greatly affect processes related to maintenance of genome integrity. One of the basic methods for studying variation in the genome, including Alu elements, is genome sequencing followed by mapping the reads to a reference genome sequence. The key feature of read alignment is the coverage of reference genome regions by mapped reads. This paper proposes a new method for analyzing the coverage of Alu elements and their adjacent regions by whole-genome sequencing reads and considers the distribution of the mean coverage between the two region types.

The natural polyphenol resveratrol exhibits anti-inflammatory, antioxidant, antitumor, and geroprotective properties. The wide range of resveratrol activities is due to its ability to modulate various signaling pathways in the cell and interact with different target molecules. Resveratrol is known to interact with DNA; however, the impact of this interaction on the chromatin structure has not been clarified. In this work, we have studied the effect of resveratrol on the structure of the nucleosome, which is the functional and structural unit of chromatin. Fluorescent microscopy of single nucleosomes based on Förster resonance energy transfer and analysis of changes in the electrophoretic mobility of nucleosomes in polyacrylamide gel have shown that resveratrol at a concentration of ~100 μM affects the conformation of DNA linker regions and limits the conformational dynamics of DNA near the nucleosome boundary but does not cause significant changes in the folding of nucleosomal DNA on the histone octamer. The small effect of resveratrol on the structure of the nucleosome compared to quercetin is presumably caused by the binding mode of resveratrol in the DNA minor groove.

The Nav1.8 sodium channels of nociceptors are involved in encoding the signals generated by multimodal nociceptors, and only a high-frequency component of this impulse response alerts the brain to tissue damage and provides information about the location and type of pain. Specific reduction of the Nav1.8 functional activity should switch off the high-frequency component, thus ensuring the normal functions of multimodal mechanoreceptors, thermoreceptors, and chemoreceptors in chronic pain. Analgesics that are completely safe upon long-term administration are unavailable for treating chronic pain in medicine. Mathematical modeling based on the Hodgkin–Huxley ionic theory was performed to understand the mechanism whereby the functional activity of the Nav1.8 channel is modulated specifically and the role that the mechanism plays in primary sensory encoding of nociceptive information. The gist of the mechanism is reducing the potential sensitivity of the Nav1.8 channel by decreasing the effective charge transferred by its activation gating structure. This was shown for the first time to completely restore the normal stimulus–response function of the nociceptive neuron. Only the high-frequency component is specifically eliminated from its membrane response. The same effect can be achieved by reducing the density of slow sodium channels. However, the effect of potential pharmacological analgesics will apparently be less specific in the latter case because of their possible interactions with other members the sodium channel superfamily.

Lateral flow immunoassay (LFI) is a simple, low-cost and quick diagnostic tool to identify various diseases by detecting analytes such as antibodies, parasites, or other relevant biomarkers. However, most LFIs diagnose the infections only qualitatively. Also, the conventional LFIs, which rely on visual inspection of the test line suffer from the low-sensitivity in case of mild or early infections and might cause false-negative interpretations. Here, we report the application of thioglycolic acid (TGA) capped CdTe quantum dots (QDs) as a label to enhance the luminescence and subsequently the detection sensitivity of the LFIs for diagnosis of Malaria. The chemical route synthesis of TGA capped CdTe QDs was optimized systematically by probing optical properties of the QDs. These optimized QDs of TGA capped CdTe have been conjugated with the anti-malaria antibodies against HRP2 protein (P. falciparum) and were subsequently incorporated into the LFIs. Further, an image processing code has been developed to carry out the quantification of malaria parasites in terms of the ratio on intensities of control (C) and test (T) lines on the LFIs. The results have been compared with the standard, colloidal gold based, LFIs. It has been demonstrated that the sensitivity of the detection of malaria infection under low parasite concentration improves significantly due to enhanced luminescence of C and T lines under UV illumination, owing to the TGA capped CdTe QDs. It has also been shown that the image processing based quantification of malaria infection can reduce the chances of false-negative results under low parasite concentration and help in carrying out early diagnosis of malaria.

Radiation therapy is one of the main methods of treating malignant neoplasms, including breast cancer. However, it is known that it can lead to an increase in the number of cancer stem cells that are resistant to traditional antiегьщк medicines and are believed to be responsible for the development of relapses and metastases. Therefore, the development of means for the elimination of cancer stem cells, especially in combination with ionizing radiation, is of considerable interest. The effects of the single and combined exposure of a new series of minor-groove DNA ligands-dimeric bisbenzimidazoles DBA(n) and DBPA(n) (where n is the number of methylene groups between two bisbenzimidazole blocks) and γ-radiation on human breast cancer cells of the MCF-7 line in vitro were studied. In particular, compounds with the maximum cytotoxic effect and binding to cells were selected; the effect of the latter on the population of CD44⁺CD24^−/low cancer stem cells and radiation-induced epithelial–mesenchymal transition was studied according to the criterion of vimentin expression. An increase in the expression level of this protein and, at the same time, the relative number of cancer stem cells after a single exposure to γ-radiation at a dose of 4 Gy was shown. DBPA(1,4) in combination with irradiation blocked radiation-induced expression of vimentin and reduced the relative number of cancer stem cells by 1.7 and 4.1 times compared with irradiation alone, respectively (p = 0.041 and p = 0.005). At the same time, the absolute number of cancer stem cells decreased by 2.8 and 12.0 times compared to irradiation alone, respectively (p = 0.029 and p = 0.004). The single and combined effect of DBA(5,7) with gamma radiation increased the expression of vimentin; the same compounds, when combined with irradiation, increased the relative number of cancer stem cells by 3.1 and 3.6 times compared with irradiation alone, respectively (p = 0.006 and p = 0.005). The absolute number of cancer stem cells increased by 2.2 and 1.5 times, respectively (p = 0.017 and p = 0.032). The data we obtained demonstrated a close relationship between the process of epithelial–mesenchymal transition and the formation of a pool of cancer stem cells after radiation exposure; they also indicated the prospects for further study of DBPA(1,4) as a means of eliminating cancer stem cells in vivo.