Background. Insight into blood viscosity in terms of its physical and biochemical properties carries significant clinical value. By understanding the relationship between the physical properties of ...blood and physiology, a potentially powerful tool for diagnosing early signs of many diseases can be discovered.
Purpose. To identify the effect of fibrinogen on tensio- and rheometric characteristics of blood plasma and serum in patients with coronary heart disease and with mitral and/or aortic valve disease.
Materials and methods. Prospective non-randomized study. The study of dynamic, equilibrium surface tension and viscoelastic modulus was performed by the pendant drop method using a PAT-1 device (Sinterface Technologies, Germany). We measured parameters characterizing the surface tension and dilatation rheology of blood serum such as: dynamic surface tension at an adsorption time of 100 s (γ), equilibrium surface tension (γ ∞) (adsorption time 2500 s), viscoelastic modulus |E|, and phase angle (φ) at frequencies of 0.1 and 0.01 Hz.
All patients under study were divided into 3 groups. The healthy volunteers (30 subjects) without chronic diseases and active complaints aged 49 to 78 years (mean age, 61.1±1.1 years) comprised the comparison group (group 1).
Group 2 - 40 patients with coronary heart disease (CHD) aged 49 to 77 years (mean age 62.2±1.3 years) who underwent bypass surgery to treat atherosclerotic coronary vessels (2 to 5 bypasses).
Group 3 - 30 patients with cardiac mitral and/or aortic valve lesions aged 52 to 78 years (mean age 61.3±1.2 years). They underwent mitral and/or aortic valve replacement with mechanical prostheses.
The most common pathophysiological syndrome in patients due to coronary artery or heart valve lesions was chronic heart failure (CHF) (stage 2A-2B according to Vasilenko-Strazhesko classification).
Results. Characteristic γ100s of blood serum and plasma had significant difference in both patients’ groups, possibly due to the role of coagulation and anti-coagulation system proteins’ role in dynamic surface tension of plasma in a shorter timeframe (up to 100 s.). The increase in Δγ100s in both patients’ groups by day 7 of the postoperative period indicates an increasing dynamic surface tension of serum compared to plasma. Plasma of perioperative patients does not differ from the comparison group by its surface-equilibrium properties. Accordingly, the Δγ∞s values in groups 1 and 2 both before surgery and on days 1 and 7 of the postoperative period are almost identical, pointing to no difference in the amount of surfactants tending to adsorb on the droplet surface. Alterations of viscoelastic modulus |E| and phase angle (φ) at 0.1 and 0.01 Hz in the perioperative period indicate changes in qualitative and quantitative characteristics of circulating blood with variation in individual homeostasis characteristics, resulting in an increase in surface elasticity combined with an almost unchanged surface viscosity.
Conclusion. Dynamic and equilibrium surface tension parameters in patients’ plasma differ from those in serum due to the presence of fibrinogen and other proteins of the blood coagulation system.
Novel disulfide-containing polypeptide toxin was discovered in the venom of the Tibellus oblongus spider. We report on isolation, spatial structure determination and electrophysiological ...characterization of this 41-residue toxin, called ω-Tbo-IT1. It has an insect-toxic effect with LD50 19 μg/g in experiments on house fly Musca domestica larvae and with LD50 20 μg/g on juvenile Gromphadorhina portentosa cockroaches. Electrophysiological experiments revealed a reversible inhibition of evoked excitatory postsynaptic currents in blow fly Calliphora vicina neuromuscular junctions, while parameters of spontaneous ones were not affected. The inhibition was concentration dependent, with IC50 value 40 ± 10 nM and Hill coefficient 3.4 ± 0.3. The toxin did not affect frog neuromuscular junctions or glutamatergic and GABAergic transmission in rat brains. Ca(2+) currents in Calliphora vicina muscle were not inhibited, whereas in Periplaneta americana cockroach neurons at least one type of voltage gated Ca(2+) current was inhibited by ω-Tbo-IT1. Thus, the toxin apparently acts as an inhibitor of presynaptic insect Ca(2+) channels. Spatial structure analysis of the recombinant ω-Tbo-IT1 by NMR spectroscopy in aqueous solution revealed that the toxin comprises the conventional ICK fold containing an extended β-hairpin loop and short β-hairpin loop which are capable of making "scissors-like mutual motions".
The products of the oxidative coupling of phenols are frequently used as synthetic analogues to natural humic substances (HS) for biomedical research. However, their molecular compositions and exact ...structures remain largely unknown. The objective of this study was to develop a novel approach for the molecular-level analysis of phenolic polymerisates that is capable of inventorying molecular constituents and resolving their distinct structural formulas. For this purpose, we have synthesized the model HS using the oxidative coupling of a specifically designed phenylpropanoic monomer, 3-(4-hydroxy-3-methoxyphenyl)-3-oxopropionic acid, to hydroquinone. We have characterized the synthesized model HS using high resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS), (1)H NMR spectroscopy, and controllable hydrogen/deuterium (H/D) exchange. We succeeded in the molecular inventory of the model HS. The assigned molecular formulas occupied the substantial space of CHO compositions in the Van Krevelen diagram with a maximum density found in the regions of tannins and lignins, resembling those of natural HS. To identify the exact structural formulas of the individual constituents in the model HS, we have applied selective H/D exchange of non-labile backbone protons by a choice of basic or acidic catalytic conditions followed by FTICR MS. The determined formulas allowed us to verify the proposed pathways of hydroxylation and carboxylation in the course of the phenolic coupling and to identify the acetylation of aromatic rings as an important side reaction. We conclude that the proposed analytical approach may be used to identify the molecular carriers of biological activity within the phenolic polymerisates and eventually within natural HS.
Global climate change is one of the most important scientific, societal and economic contemporary challenges. Fundamental understanding of the major
processes driving climate change is the key ...problem which is to be solved not only on a global but also on a regional scale. The accuracy of regional
climate modelling depends on a number of factors. One of these factors is the adequate and comprehensive information on the anthropogenic impact
which is highest in industrial regions and areas with dense population – modern megacities. Megacities are not only “heat islands”, but also
significant sources of emissions of various substances into the atmosphere, including greenhouse and reactive gases. In 2019, the mobile experiment
EMME (Emission Monitoring Mobile Experiment) was conducted within the St. Petersburg agglomeration (Russia) aiming to estimate the emission
intensity of greenhouse (CO2, CH4) and reactive (CO, NOx) gases for St. Petersburg, which is the largest
northern megacity. St. Petersburg State University (Russia), Karlsruhe Institute of Technology (Germany) and the University of Bremen (Germany)
jointly ran this experiment. The core instruments of the campaign were two portable Bruker EM27/SUN Fourier
transform infrared (FTIR) spectrometers which were used for
ground-based remote sensing measurements of the total column amount of CO2, CH4 and CO at upwind and downwind locations on
opposite sides of the city. The NO2 tropospheric column amount was observed along a circular highway around the city by continuous mobile
measurements of scattered solar visible radiation with an OceanOptics HR4000 spectrometer using the differential optical absorption spectroscopy (DOAS) technique. Simultaneously, air samples were
collected in air bags for subsequent laboratory analysis. The air samples were taken at the locations of FTIR observations at the ground level and
also at altitudes of about 100 m when air bags were lifted by a kite (in case of suitable landscape and favourable wind conditions). The
entire campaign consisted of 11 mostly cloudless days of measurements in March–April 2019. Planning of measurements for each day included the
determination of optimal location for FTIR spectrometers based on weather forecasts, combined with the numerical modelling of the pollution transport
in the megacity area. The real-time corrections of the FTIR operation sites were performed depending on the actual evolution of the megacity
NOx plume as detected by the mobile DOAS observations. The estimates of the St. Petersburg emission intensities for the
considered greenhouse and reactive gases were obtained by coupling a box model and the results of the EMME observational campaign using the mass
balance approach. The CO2 emission flux for St. Petersburg as an area source was estimated to be 89 ± 28 ktkm-2yr-1,
which is 2 times higher than the corresponding value in the EDGAR database. The experiment revealed the CH4 emission flux of
135 ± 68 tkm-2yr-1, which is about 1 order of magnitude greater than the value reported by the official inventories of
St. Petersburg emissions (∼ 25 tkm-2yr-1 for 2017). At the same time, for the urban territory of St. Petersburg, both the
EMME experiment and the official inventories for 2017 give similar results for the CO anthropogenic flux
(251 ± 104 tkm-2yr-1 vs. 410 tkm-2yr-1) and for the NOx anthropogenic flux
(66 ± 28 tkm-2yr-1 vs. 69 tkm-2yr-1).
Here, we report a novel approach to enumeration of carboxylic groups carried by individual molecules of humic substances using selective chemical modification and isotopic labeling ...(deuteromethylation) and high-resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FTICR MS). Esterification was conducted with a use of thionyl chloride–deuteromethanol reagent under mild conditions to avoid transesterification. The deuteromethylated products were subjected to solid phase extraction using PPL Bond Elute cartridges prior to FTICR MS analysis. An amount of carboxyl groups in the individual molecular component was estimated from the length of identified deuteromethylation series. The method allowed for discerning between compounds with close elemental compositions possessing different protolytic properties. We found that different carboxylic moieties occupy distinct regions in molecular space of humic substances (HS) projected onto Van Krevelen diagram. These locations do not depend on the source of the humic material and can be assigned to carboxyl-rich alicyclic molecules (5 to 6 COOH), hydrolyzable tannins (3-4 COOH), lignins (1 to 2 COOH), condensed tannins and lignans (0 to 1 COOH), and carbohydrates (0 COOH). At the same time, the alignment pattern of these carboxylated species along the structural evolution lines in Van Krevelen diagrams was characteristic to the specific transformation processes undergone by the humic materials in the different environments. The obtained data enable mapping of molecular ensemble of HS with regards to their specific acidic compartments and might be used for directed fractionation of HS.
Graphical abstract
Selective isotopic labeling followed by FTICR MS enables discerning between humic molecules with close elemental compositions carrying different numbers of carboxylic groups.
Pro- and mature neurotrophins often elicit opposing biological effects. For example, mature brain-derived neurotrophic factor (mBDNF) is critical for long-term potentiation induced by high-frequency ...stimulation, whereas proBDNF facilitate long-term depression induced by low-frequency stimulation. Because mBDNF is derived from proBDNF by endoproteolytic cleavage, mechanisms regulating the cleavage of proBDNF may control the direction of BDNF regulation. Using methods that selectively detect proBDNF or mBDNF, we show that low-frequency stimulation induced predominant proBDNF secretion in cultured hippocampal neurons. In contrast, high-frequency stimulation preferentially increased extracellular mBDNF. Inhibition of extracellular, but not intracellular cleavage of proBDNF greatly reduced high-frequency stimulation-induced extracellular mBDNF. Moreover, high-frequency, but not low-frequency stimulation selectively induced the secretion of tissue plasminogen activator, a key protease involved in extracellular proBDNF to mBDNF conversion. Thus, high-frequency neuronal activity controls the ratio of extracellular proBDNF/mBDNF by regulating the secretion of extracellular proteases. Our study demonstrates activity-dependent control of extracellular proteolytic cleavage of a secretory protein, and reveals an important mechanism that controls diametrically opposed functions of BDNF isoforms.
HIV-1 entry into host cells starts with interactions between the viral envelope glycoprotein (Env) and cellular CD4 receptors and coreceptors. Previous work has suggested that efficient HIV entry ...also depends on intracellular signaling, but this remains controversial. Here we report that formation of the pre-fusion Env-CD4-coreceptor complexes triggers non-apoptotic cell surface exposure of the membrane lipid phosphatidylserine (PS). HIV-1-induced PS redistribution depends on Ca2+ signaling triggered by Env-coreceptor interactions and involves the lipid scramblase TMEM16F. Externalized PS strongly promotes Env-mediated membrane fusion and HIV-1 infection. Blocking externalized PS or suppressing TMEM16F inhibited Env-mediated fusion. Exogenously added PS promoted fusion, with fusion dependence on PS being especially strong for cells with low surface density of coreceptors. These findings suggest that cell-surface PS acts as an important cofactor that promotes the fusogenic restructuring of pre-fusion complexes and likely focuses the infection on cells conducive to PS signaling.
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•HIV-cell binding triggers phosphatidylserine (PS) exposure at the cell surface•PS exposure depends on gp120-coreceptor interactions, Ca2+ signaling, and TMEM16F•Suppression of PS exposure inhibits Env restructuring, viral fusion, and infection•PS signaling, a hallmark of activation, facilitates HIV entry
Zaitseva et al. show that HIV binding to target cells induces signaling that leads to exposure of phosphatidylserine on the cell surface. Interaction between the viral envelope glycoprotein and phosphatidylserine facilitates receptor-dependent merger of viral and cell membranes and infection. Phosphatidylserine dependence may focus infection on cells of certain activation status.
Understanding the mechanism of entry of cationic peptides such as nona-arginine (R9) into cells remains an important challenge to their use as efficient drug-delivery vehicles. At nanomolar to low ...micromolar R9 concentrations and at physiological temperature, peptide entry involves endocytosis. In contrast, at a concentration ≥10 μM, R9 induces a very effective non-endocytic entry pathway specific for cationic peptides. We found that a similar entry pathway is induced at 1-2 μM concentrations of R9 if peptide application is accompanied by a rapid temperature drop to 15°C. Both at physiological and at sub-physiological temperatures, this entry mechanism was inhibited by depletion of the intracellular ATP pool. Intriguingly, we found that R9 at 10-20 μM and 37°C induces repetitive spikes in intracellular Ca(2+) concentration. This Ca(2+) signalling correlated with the efficiency of the peptide entry. Pre-loading cells with the Ca(2+) chelator BAPTA (1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) inhibited both Ca(2+) spikes and peptide entry, suggesting that an increase in intracellular Ca(2+) precedes and is required for peptide entry. One of the hallmarks of Ca(2+) signalling is a transient cell-surface exposure of phosphatidylserine (PS), a lipid normally residing only in the inner leaflet of the plasma membrane. Blocking the accessible PS with the PS-binding domain of lactadherin strongly inhibited non-endocytic R9 entry, suggesting the importance of PS externalization in this process. To conclude, we uncovered a novel mechanistic link between calcium signalling and entry of cationic peptides. This finding will enhance our understanding of the properties of plasma membrane and guide development of future drug-delivery vehicles.
Two hundred
three patients with essential hypertension (20- to 55-year-old men) were
examined initially and at the end of a 1-year follow-up. Clinical,
psychological, and psychophysiological methods ...were used. In the
psychophysiological assessment, systolic blood pressure (SBP), diastolic blood
pressure (DBF), heart rate, and respiratory rate were recorded at rest and
during various emotional stressors. Patients who exhibited a greater increase in
blood pressure during psychological stress, in addition to an inherited
predisposition to essential hypertension, had higher levels of assertiveness and
interpersonal conflict. The differences in cardiovascular response to various
emotional stressors depended on the psychological features of the hypertensive
patients. An SBP increase during the performance of mental arithmetic correlated
with anxiety level, whereas a DBP increase was associated with assertiveness.
Changes in SBP and DBP during a stressful computer game correlated with the
level of competitiveness and conflict. Hypertensive patients who exhibited an
increase in blood pressure during the follow-up were characterized initially by
a greater DBP increase during emotional stress and a longer recovery period.
Key words:
essential hypertension, psychophysiological interrelations, cardiovascular
reactivity
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