Oxygen dependence of metabolic fluxes and energy generation of Saccharomyces cerevisiae CEN.PK113-1A

<p>Abstract</p> <p>Background</p> <p>The yeast <it>Saccharomyces cerevisiae </it>is able to adjust to external oxygen availability by utilizing both respirative and fermentative metabolic modes. Adjusting the metabolic mode involves alteration of the intracellular metabolic fluxes that are determined by the cell's multilevel regulatory network. Oxygen is a major determinant of the physiology of <it>S. cerevisiae </it>but understanding of the oxygen dependence of intracellular flux distributions is still scarce.</p> <p>Results</p> <p>Metabolic flux distributions of <it>S. cerevisiae </it>CEN.PK113-1A growing in glucose-limited chemostat cultures at a dilution rate of 0.1 h^-1with 20.9%, 2.8%, 1.0%, 0.5% or 0.0% O₂in the inlet gas were quantified by ¹³C-MFA. Metabolic flux ratios from fractional [U-¹³C]glucose labelling experiments were used to solve the underdetermined MFA system of central carbon metabolism of <it>S. cerevisiae</it>.</p> <p>While ethanol production was observed already in 2.8% oxygen, only minor differences in the flux distribution were observed, compared to fully aerobic conditions. However, in 1.0% and 0.5% oxygen the respiratory rate was severely restricted, resulting in progressively reduced fluxes through the TCA cycle and the direction of major fluxes to the fermentative pathway. A redistribution of fluxes was observed in all branching points of central carbon metabolism. Yet only when oxygen provision was reduced to 0.5%, was the biomass yield exceeded by the yields of ethanol and CO₂. Respirative ATP generation provided 59% of the ATP demand in fully aerobic conditions and still a substantial 25% in 0.5% oxygenation. An extensive redistribution of fluxes was observed in anaerobic conditions compared to all the aerobic conditions. Positive correlation between the transcriptional levels of metabolic enzymes and the corresponding fluxes in the different oxygenation conditions was found only in the respirative pathway.</p> <p>Conclusion</p> <p>¹³C-constrained MFA enabled quantitative determination of intracellular fluxes in conditions of different redox challenges without including redox cofactors in metabolite mass balances. A redistribution of fluxes was observed not only for respirative, respiro-fermentative and fermentative metabolisms, but also for cells grown with 2.8%, 1.0% and 0.5% oxygen. Although the cellular metabolism was respiro-fermentative in each of these low oxygen conditions, the actual amount of oxygen available resulted in different contributions through respirative and fermentative pathways.</p

Evaluating the Solar Slowly Varying Component at C-Band Using Dual- and Single-Polarization Weather Radars in Europe

Six C-band weather radars located in Europe (Finland, Netherlands, and Switzerland) have been used to monitor the slowly varying solar emission, which is an oscillation with an amplitude of several decibels and a period of approximately 27 days. It is caused by the fact that the number of active regions that enhance the solar radio emission with respect to the quiet component, as seen from Earth, varies because of the Sun’s rotation about its axis. The analysis is based on solar signals contained in the polar volume data produced during the operational weather scan strategy. This paper presents hundreds of daily comparisons between radar estimates and the Sun’s reference signal, during the current active Sun period (year 2014). The Sun’s reference values are accurately measured by the Dominion Radio Astrophysical Observatory (DRAO) at S-band and converted to C-band using a standard DRAO formula. Vertical and horizontal polarization receivers are able to capture the monthly oscillation of the solar microwave signal: the standard deviation of the log-transformed ratio between radars and the DRAO reference ranges from 0.26 to 0.4 dB. A larger coefficient (and a different value for the quiet Sun component) in the standard formula improves the agreement

Pilot study of propofol-induced slow waves as a pharmacologic test for brain dysfunction after brain injury

Abstract Background: Slow waves (&lt; 1 Hz) are the most important electroencephalogram signatures of non-rapid eye movement sleep. While considered to have a substantial importance in, for example, providing conditions for single-cell rest and preventing long-term neural damage, a disturbance in this neurophysiological phenomenon is a potential indicator of brain dysfunction. Methods: Since, in healthy individuals, slow waves can be induced with anesthetics, we tested the possible association between hypoxic brain injury and slow wave activity in comatose post-cardiac arrest patients (N = 10) using controlled propofol exposure. The slow wave activity was determined by calculating the low-frequency (&lt; 1 Hz) power of the electroencephalograms recorded approximately 48 h after cardiac arrest. To define the association between the slow waves and the potential brain injury, the patients’ neurological recovery was then followed for six months. Results: In the patients with good neurological outcome (N = 6), the low-frequency power of electroencephalogram representing the slow wave activity was found to substantially increase (190 ± 83%, mean ± SD) due to the administration of propofol. By contrast, the patients with poor neurological outcome (N = 4) were unable to generate propofol-induced slow waves. Conclusions: In this experimental pilot study, the comatose post-cardiac arrest patients with poor neurological outcome were unable to generate normal propofol-induced electroencephalographic slow wave activity 48 h after cardiac arrest. The finding might offer potential for developing a pharmacological test for prognostication of brain injury by measuring the electroencephalographic response to propofol

Using Hilbert-Huang transform to assess EEG slow wave activity during anesthesia in post-cardiac arrest patients

Abstract Hypoxic ischemic encephalopathy (HIE) is a severe consequence of cardiac arrest (CA) representing a substantial diagnostic challenge. We have recently designed a novel method for the assessment of HIE after CA. The method is based on estimating the severity of the brain injury by analyzing changes in the electroencephalogram (EEG) slow wave activity while the patient is exposed to an anesthetic drug propofol in a controlled manner. In this paper, Hilbert-Huang Transform (HHT) was used to analyze EEG slow wave activity during anesthesia in ten post-CA patients. The recordings were made in the intensive care unit 36–48 hours after the CA in an experiment, during which the propofol infusion rate was incrementally decreased to determine the drug-induced changes in the EEG at different anesthetic levels. HHT was shown to successfully capture the changes in the slow wave activity to the behavior of intrinsic mode functions (IMFs). While, in patients with good neurological outcome defined after a six-month control period, propofol induced a significant increase in the amplitude of IMFs representing the slow wave activity, the patients with poor neurological outcome were unable to produce such a response. Consequently, the proposed method offer substantial prognostic potential by providing a novel approach for early estimation of HIE after CA