Oscillations of Hemodynamic Parameters Induced by Negative Pressure Breathing in Healthy Humans.

INTRODUCTION: Negative pressure breathing is breathing with decreased pressure in the respiratory tract without lowering pressure acting on the torso. We lowered air pressure only during inspiration (NPBin). NPBin, used to increase venous return to the heart, is considered a countermeasure against redistribution of body fluids toward the head during spaceflight. We studied NPBin effects on circulation in healthy humans with an emphasis on NPBin-induced oscillations of hemodynamic parameters synchronous with breathing. We propose an approach to analyze the oscillations based on coherent averaging.METHODS: Eight men ages 24-42 yr participated in the NPBin and control series. During the series, to reproduce fluids shift observed under microgravity, subjects were supine and head down (-8°). Duration of NPBin was 20 min, rarefaction -20 cm H2O. Hemodynamic parameters were measured by Finometer. Electrical impedance measurements were used to estimate changes in blood filling of cerebral vessels.RESULTS: Mean values of hemodynamic parameters virtually did not change under NPBin, but NPBin induced oscillations of the parameters synchronous with respiration. Peak-to-peak amplitude under NPBin were: mean arterial pressure, 4 ± 1 (mmHg); stroke volume, 7 ± 3 (mL); and heart rate, 4 ± 1 (bpm). Electrical impedance of the head increased during inspiration. The increase under NPBin was three times greater than under normal breathing.DISCUSSION: Analysis of oscillations gives more information than analysis of mean values. NPBin induces short-term decrease in left ventricle stroke volume and arterial blood pressure during each inspiration; the decrease is compensated by increase after inspiration. NPBin facilitates redistribution of body fluids away from the head.Semenov YS, Melnikov IS, Luzhnov PV, Dyachenko AI. Oscillations of hemodynamic parameters induced by negative pressure breathing in healthy humans. Aerosp Med Hum Perform. 2024; 95(6):297-304.

Small-angle X-ray scattering structural insights into alternative pathway of actin oligomerization associated with inactivated state.

In addition to the well-known monomeric globular (G-actin) and polymeric fibrillar (F-actin) forms, actin can exist in the so-called inactivated form (I-actin). Hsp70 chaperon, prefoldin, and CCT chaperonin are required to obtain native globular state. In contrast, I-actin is spontaneously formed in the absence of intracellular folding machinery. I-actin can be obtained from G-actin by elimination of divalent ion, incubation in presence of small concentrations of denaturants, and by heat exposure. Since G-actin is a quasi-stationary, thermodynamically unstable form, it can gradually transform into inactivated state in the absence of chelating/denaturating agents or heat exposure, but the transition is much slower. I-actin was shown to associate into oligomers up to the molecular weight of 14-16 G-actin monomers, though the structure of these oligomers remains uncharacterized. This study employs small-angle X-ray scattering to reveal novel insights into the oligomerization process of such spontaneously formed inactivated actin. These oligomers are differentiated from F-actin through comparative analysis, highlighting a unique oligomerization pathway.

I-Shaped Dimers of a Plant Chloroplast FOF1-ATP Synthase in Response to Changes in Ionic Strength.

F-type ATP synthases play a key role in oxidative and photophosphorylation processes generating adenosine triphosphate (ATP) for most biochemical reactions in living organisms. In contrast to the mitochondrial FOF1-ATP synthases, those of chloroplasts are known to be mostly monomers with approx. 15% fraction of oligomers interacting presumably non-specifically in a thylakoid membrane. To shed light on the nature of this difference we studied interactions of the chloroplast ATP synthases using small-angle X-ray scattering (SAXS) method. Here, we report evidence of I-shaped dimerization of solubilized FOF1-ATP synthases from spinach chloroplasts at different ionic strengths. The structural data were obtained by SAXS and demonstrated dimerization in response to ionic strength. The best model describing SAXS data was two ATP-synthases connected through F1/F1' parts, presumably via their δ-subunits, forming "I" shape dimers. Such I-shaped dimers might possibly connect the neighboring lamellae in thylakoid stacks assuming that the FOF1 monomers comprising such dimers are embedded in parallel opposing stacked thylakoid membrane areas. If this type of dimerization exists in nature, it might be one of the pathways of inhibition of chloroplast FOF1-ATP synthase for preventing ATP hydrolysis in the dark, when ionic strength in plant chloroplasts is rising. Together with a redox switch inserted into a γ-subunit of chloroplast FOF1 and lateral oligomerization, an I-shaped dimerization might comprise a subtle regulatory process of ATP synthesis and stabilize the structure of thylakoid stacks in chloroplasts.

Anti-Stokes fluorescence excitation reveals conformational mobility of the C-phycocyanin chromophores.

The structural organization of natural pigment-protein complexes provides a specific environment for the chromophore groups. Yet, proteins are inherently dynamic and conformationally mobile. In this work, we demonstrate the heterogeneity of chromophores of C-phycocyanin (C-PC) from Arthrospira platensis. Part of the population of trimeric C-PC is subject to spontaneous disturbances of protein-protein interactions resulting in increased conformational mobility of the chromophores. Upon fluorescence excitation in the visible range, the spectral signatures of these poorly populated states are masked by bulk chromophore states, but the former could be clearly discriminated when the fluorescence is excited by near-infrared quanta. Such selective excitation of conformationally mobile C-PC chromophores is due to the structure of their S1 level, which is characterized by a significantly broadened spectral line. We demonstrate that the anti-Stokes C-PC fluorescence is the result of single-photon absorption. By combining spectral and structural methods, we characterize four distinct states of C-PC chromophores emitting at 620, 650, 665, and 720 nm and assigned the fast component in the anti-Stokes fluorescence decay kinetics in the range of 690-750 nm to the chromophores with increased conformational mobility. Our data suggest that the spectral and temporal characteristics of the anti-Stokes fluorescence can be used to study protein dynamics and develop methods to visualize local environment parameters such as temperature.

On optimal and suboptimal treatment strategies for a mathematical model of leukemia.

In this work an optimization problem for a leukemia treatment model based on the Gompertzian law of cell growth is considered. The quantities of the leukemic and of the healthy cells at the end of the therapy are chosen as the criterion of the treatment quality. In the case where the number of healthy cells at the end of the therapy is higher than a chosen desired number, an analytical solution of the optimization problem for a wide class of therapy processes is given. If this is not the case, a control strategy called alternative is suggested.