Increased cardiac production of dihydroxyphenylalanine (DOPA) during sympathetic stimulation in anaesthetized dogs.

Entry of dihydroxyphenylalanine (DOPA) into plasma from specific organs may reflect regional activity of tyrosine hydroxylase, the enzyme responsible for the immediate synthesis of DOPA and rate-limiting for subsequent formation of catecholamines. Therefore, cardiac spillovers of DOPA, noradrenaline and the intraneuronal metabolite of noradrenaline, dihydroxyphenylglycol (DHPG), were examined during two periods of graded electrical stimulation of the sympathetic nerves to the heart in anesthetized dogs. Responses were examined before and after neuronal uptake blockade with desipramine. Cardiac spillover of DOPA increased by 1.8- and 4.4-fold during sympathetic stimulation before desipramine and by 1.6- and 3.3-fold after desipramine. Fold increases in cardiac spillover of DOPA were much lower than but positively related with fold increases in noradrenaline spillover (5.9- and 13.8-fold increases before and 9.0- and 15.8-fold increases after desipramine). Increases in cardiac spillover of DHPG (1.5- and 2.3-fold increases) were blocked by desipramine so that fold changes in spillover of DOPA were greater than and poorly related to changes in spillover of DHPG. Fold increases in cardiac spillover of DOPA showed a close one-to-one positive relationship with fold increases in the sum of cardiac spillovers of noradrenaline and dihydroxyphenylglycol before and after desipramine. For a given fold increase in noradrenaline release, transmitter turnover is increased fractionally and noradrenaline synthesis need also only increase fractionally to maintain transmitter stores constant. The close relationship between fold increases in cardiac spillover of DOPA and combined spillovers of noradrenaline and DHPG is consistent with regulation of tyrosine hydroxylase activity to match changes in noradrenaline synthesis with changes in noradrenaline turnover. Changes in cardiac spillover of DOPA appear to reflect local changes in tyrosine hydroxylase activity.     

Plant Phenomics: Fundamental Bases,Software and Hardware Platforms,and Machine Learning

Russian Journal of Plant Physiology - In recent years, a new branch of plant physiology, plant phenomics, which focuses on identifying patterns of organization and changes in plant Phenomes, i.e.,...     

Enhanced central and conduit pulmonary arterial reservoir function offsets reduced ductal systolic outflow during constriction of the fetal ductus arteriosus

Constriction of the fetal ductus arteriosus (DA) has disparate effects on mean and phasic hemodynamics, as mean DA blood flow is preserved until constriction is severe, but DA systolic and diastolic blood velocities change with only mild constriction. To determine the basis of this disparity and its physiological significance, seven anesthetized late-gestation fetal sheep were instrumented with pulmonary trunk (PT), DA, and left pulmonary artery (PA) micromanometer catheters and transit-time flow probes. Blood flow profile and wave intensity analyses were performed at baseline and during mild, moderate, and severe DA constriction (defined as pulmonary-aortic mean pressure differences of 4, 8, and 14 mmHg, respectively), produced with an adjustable snare. With DA constriction, mean DA flow was initially maintained but decreased with severe constriction (P < 0.05) in conjunction with a reduction (P < 0.05) in PT flow (i.e., right ventricular output). By contrast, DA systolic flow fell progressively during DA constriction (P < 0.001), due to decreased transmission of both early and midsystolic proximal flow-enhancing forward-running compression waves into the DA. However, DA constriction was also accompanied by greater systolic storage of blood in the PT and main PA (P < 0.025), and increased retrograde diastolic flow from compliant major branch PA (P < 0.001). Transductal discharge of these central and conduit PA blood reservoirs in diastole offset systolic DA flow reductions. These data suggest that, during DA constriction in the fetus, enhanced central and conduit PA reservoir function constitutes an important compensatory mechanism that contributes to preservation of mean DA flow via a systolic-to-diastolic redistribution of phasic DA flow.     

Simultaneous pulmonary trunk and pulmonary arterial wave intensity analysis in fetal lambs: evidence for cyclical, midsystolic pulmonary vasoconstriction

The physiological basis of a characteristically low blood flow to the fetal lungs is incompletely understood. To determine the potential role of pulmonary vascular interaction in this phenomenon, simultaneous wave intensity analysis (WIA) was performed in the pulmonary trunk (PT) and left pulmonary artery (LPA) of 10 anesthetized late-gestation fetal sheep instrumented with PT and LPA micromanometer catheters to measure pressure (P) and transit-time flow probes to obtain blood velocity (U). Studies were performed at rest and during brief complete occlusion of the ductus arteriosus to augment pulmonary vasoconstriction (n = 4) or main pulmonary artery to abolish wave transmission from the lungs (n = 3). Wave intensity (dI(W)) was calculated as the product of the P and U rates of change. Forward and backward components of dI(W) were determined after calculation of wave speed. PT and LPA WIA displayed an early systolic forward compression wave (FCW(is)) increasing P and U, and a late systolic forward expansion wave decreasing P and U. However, a marked midsystolic fall in LPA U to near-zero was related to an extremely prominent midsystolic backward compression wave (BCW(ms)) that arose approximately 5 cm distal to the LPA, was threefold larger than the PT BCW(ms) (P < 0.001), of similar size to FCW(is) at rest (P > 0.6), larger than FCW(is) following ductal occlusion (P < 0.05) and abolished after main pulmonary artery occlusion. These findings suggest that the absence of pulmonary arterial midsystolic forward flow which accompanies a low fetal lung blood flow is due to a BCW(ms) generated in part by cyclical vasoconstriction within the pulmonary microcirculation.     

Engineered silver nanoparticles are sensed at the plasma membrane and dramatically modify the physiology of Arabidopsis thaliana plants

Silver nanoparticles (Ag NPs) are the world's most important nanomaterial and nanotoxicant. The aim of this study was to determine the early stages of interactions between Ag NPs and plant cells, and to investigate their physiological roles. We have shown that the addition of Ag NPs to cultivation medium, at levels above 300 mg L^?1, inhibited Arabidopsis thaliana root elongation and leaf expansion. This also resulted in decreased photosynthetic efficiency and the extreme accumulation of Ag in tissues. Acute application of Ag NPs induced a transient elevation of [Ca²⁺]_cyt and the accumulation of reactive oxygen species (ROS; partially generated by NADPH oxidase). Whole‐cell patch‐clamp measurements on root cell protoplasts demonstrated that Ag NPs slightly inhibited plasma membrane K⁺ efflux and Ca²⁺ influx currents, or caused membrane breakdown; however, in excised outside‐out patches, Ag NPs activated Gd³⁺‐sensitive Ca²⁺ influx channels with unitary conductance of approximately 56 pS. Bulk particles did not modify the plasma membrane currents. Tests with electron paramagnetic resonance spectroscopy showed that Ag NPs were not able to catalyse hydroxyl radical generation, but that they directly oxidized the major plant antioxidant, l ‐ascorbic acid. Overall, the data presented shed light on mechanisms of the impact of nanosilver on plant cells, and show that these include the induction of classical stress signalling reactions (mediated by [Ca²⁺]_cyt and ROS) and a specific effect on the plasma membrane conductance and the reduced ascorbate.     

Sheep cardiac Purkinje fibers: Configurational changes during the cardiac cycle

Previous attempts to study the cytoarchitecture of cardiac Purkinje fibers with the scanning electron microscope (SEM) have been limited by the surrounding dense connective tissue. In this study the connective tissue was removed by treatment with 8N HCl, after adult sheep hearts were fixed in diastole or systole and tissue taken for SEM and transmission electron microscopy (TEM). In SEM, Purkinje fibers freely anastomosed in false tendons and formed a subendocardial plexus. In systole, medium and small-sized Purkinje fibers formed deep clefts not observed in diastole. The clefts are thought to be due to sarcolemmal folding and fiber buckling and may therefore affect conduction. The myofibrils beneath the laterally apposed sarcolemmas of adjacent Purkinje cells when fixed in systole were often observed as tightly curved arches in series. Similar configurations with expanded arches were observed in diastole. The formation of arches by myofibrils is unique to Purkinje fibers and is interpreted as the mechanism responsible for their compliance to stretch. The significance of contraction in producing the observed geometric changes in Purkinje fibers and the implications of their cytoarchitecture with respect to conduction are discussed.     

Wnt family proteins are secreted and associated with the cell surface.

Members of the Wnt gene family are proposed to function in both normal development and differentiation as well as in mammary tumorigenesis. To understand the function of Wnt proteins in these two processes, we present here a biochemical characterization of seven Wnt family members. For these studies, AtT-20 cells, a neuroendocrine cell line previously shown to efficiently process and secrete Wnt-1, was transfected with expression vectors encoding Wnt family members. All of the newly characterized Wnt proteins are glycosylated, secreted proteins that are tightly associated with the cell surface or extracellular matrix. We have also identified native Wnt proteins in retinoic acid-treated P19 embryonal carcinoma cells, and they exhibit the same biochemical characteristics as the recombinant proteins. These data suggest that Wnt family members function in cell to cell signaling in a fashion similar to Wnt-1.     

Long-term development of the radionuclide exposure of murine rodent populations in Belarus after the Chernobyl accident

As a determinant of the associated health risks, the behavior of radionuclides in natural ecosystems needs to be better understood. Therefore, the activity concentration of various long-lived radionuclides released due to the Chernobyl accident, and the corresponding contributions to the whole-body dose rate, was studied as a function of time in mammalian indicator species inhabiting the natural forest ecosystems of Belarus, the bank vole (Clethrionomys glareolus) and the yellow-necked mouse (Apodemus flavicollus). The activity concentrations of ¹³⁷Cs, ¹³⁴Cs, ⁹⁰Sr, ²³⁸Pu, ^239,240Pu, ²⁴¹Pu and ²⁴¹Am in soil and in animals were measured at five monitoring sites with different ground deposition of radionuclides at different distances from the destroyed reactor. The observed temporal pattern of the radionuclide activity concentration in the studied animal populations reflects the changes in biological availability of these isotopes for biota, mostly due to fuel particle destruction and appearance of dissolved and exchangeable forms of radionuclides. The time course of ^134+137Cs activity concentrations in animal populations appeared as a sequence of increase, peak and decrease. Maximal levels of radiocesium occurred 1–2 years after deposition, followed by an exponential decrease. Concentrations of incorporated ⁹⁰Sr increased up to the tenth year after deposition. The activity concentrations of transuranic elements (²³⁸Pu, ^239,240Pu, ²⁴¹Pu and ²⁴¹Am) were much lower than those of the other radionuclides, in the studied animals. A considerable activity of ²⁴¹Am in animals from areas with high levels of contamination was firstly detected 5 years after deposition, it increased up to the tenth year and is expected to increase further in the future. Maximal values of the whole-body absorbed dose rates occurred during the year of deposition, followed by a decrease in the subsequent period. Generally, this decrease was monotonic, mainly determined by the decrease of the external γ-ray dose rate, but there were exceptions due to the delayed maximum of internal exposure. The inter-individual distributions of radionuclide concentrations and lifetime whole-body absorbed doses were asymmetric and close to log-normal, including concentrations and doses considerably higher than the population mean values.     

Lack of the antioxidant glutathione peroxidase-1 does not increase atherosclerosis in C57BL/J6 mice fed a high-fat diet

Oxidative stress is thought to contribute to the initiation and progression of atherosclerosis. As glutathione peroxidase-1 (Gpx1) is an antioxidant enzyme that detoxifies lipid hydroperoxides, we tested the impact of Gpx1 deficiency on atherosclerotic processes and antioxidant enzyme expression in mice fed a high-fat diet (HFD). After 12 weeks of HFD, atherosclerotic lesions at the aortic sinus were of similar size in control and Gpx1-deficient mice. However, after 20 weeks of HFD, lesion size increased further in control but not in Gpx1-deficient mice, even though plasma and aortic wall markers of oxidative damage did not differ between groups. In control mice, the expression of Gpx1 increased and that of Gpx3 decreased at the aortic sinus after 20 weeks of HFD, with no change in the expression of Gpx2, Gpx4, catalase, peroxiredoxin-6, glutaredoxin-1 and -2, or thioredoxin-1 and -2. By comparison, in Gpx1-deficient mice, the expression of antioxidant genes was unaltered except for a decrease in glutaredoxin-1 and an increase in glutaredoxin-2. These changes were associated with increased expression of the proinflammatory marker monocyte chemoattractant protein-1 in control mice but not in Gpx1-deficient mice. In summary, a specific deficiency in Gpx1 was not accompanied by an increase in markers of oxidative damage or increased atherosclerosis in a murine model of HFD-induced atherogenesis.     

Increased right ventricular output and central pulmonary reservoir function support rise in pulmonary blood flow during adenosine infusion in the ovine fetus

Although adenosine markedly increases fetal pulmonary blood flow, the specific changes in pulmonary trunk (PT), ductus arteriosus (DA), and conduit pulmonary artery (PA) flow interactions that support this increased flow are unknown. To address this issue, seven anesthetized late-gestation fetal sheep were instrumented with PT, DA, and left PA micromanometer catheters and transit-time flow probes. Blood flow profile and wave intensity analyses were performed at baseline and after adenosine infusion to increase PA flow approximately fivefold. With adenosine infusion, DA mean and phasic flows were unchanged, but increases in mean PT (500 ± 256 ml/min, P = 0.002) and the combined left and right PA flow (479 ± 181 ml/min, P < 0.001) were similar (P > 0.7) and related to a larger flow-increasing forward-running compression wave arising from right ventricular (RV) impulsive contraction. Moreover, while the increased PT flow was confined to systole, the rise in PA flow spanned systole (316 ml/min) and diastole (163 ml/min). This elevated PA diastolic flow was accompanied by a 170% greater discharge from a PT and main PA reservoir filled in systole (P < 0.001), but loss of retrograde blood discharge from a conduit PA reservoir that was evident at baseline. These data suggest that 1) an increase in fetal pulmonary blood flow produced by adenosine infusion is primarily supported by a higher PT blood flow (i.e., RV output); 2) about two-thirds of this increased RV output passes into the pulmonary circulation during systole; and 3) the remainder is transiently stored in a central PT and main PA systolic reservoir, from where it discharges into the lungs in diastole.