Modulation of the Major Paths of Carbon in Photorespiratory Mutants of Synechocystis

Background: Recent studies using transcript and metabolite profiles of wild-type and gene deletion mutants revealed that photorespiratory pathways are essential for the growth of Synechocystis sp. PCC 6803 under atmospheric conditions. Pool size changes of primary metabolites, such as glycine and glycolate, indicated a link to photorespiration. Methodology/Principal Findings: The C-13 labelling kinetics of primary metabolites were analysed in photoautotrophically grown cultures of Synechocystis sp. PCC 6803 by gas chromatography-mass spectrometry (GC-MS) to demonstrate the link with photorespiration. Cells pre-acclimated to high CO2 (5%, HC) or limited CO2 (0.035%, LC) conditions were pulse-labelled under very high (2% w/w) C-13-NaHCO3 (VHC) conditions followed by treatment with ambient C-12 at HC and LC conditions, respectively. The C-13 enrichment, relative changes in pool size, and C-13 flux of selected metabolites were evaluated. We demonstrate two major paths of CO2 assimilation via Rubisco in Synechocystis, i.e., from 3PGA via PEP to aspartate, malate and citrate or, to a lesser extent, from 3PGA via glucose-6-phosphate to sucrose. The results reveal evidence of carbon channelling from 3PGA to the PEP pool. Furthermore, C-13 labelling of glycolate was observed under conditions thought to suppress photorespiration. Using the glycolate-accumulating Delta glcD1 mutant, we demonstrate enhanced C-13 partitioning into the glycolate pool under conditions favouring photorespiration and enhanced C-13 partitioning into the glycine pool of the glycine-accumulating Delta gcvT mutant. Under LC conditions, the photorespiratory mutants Delta glcD1 and Delta gcvT showed enhanced activity of the additional carbon-fixing PEP carboxylase pathway. Conclusions/Significance: With our approach of non-steady-state C-13 labelling and analysis of metabolite pool sizes with respective C-13 enrichments, we identify the use and modulation of major pathways of carbon assimilation in Synechocystis in the presence of high and low inorganic carbon supplies

Danger control programs cause tissue injury and remodeling.

Are there common pathways underlying the broad spectrum of tissue pathologies that develop upon injuries and from subsequent tissue remodeling? Here, we explain the pathophysiological impact of a set of evolutionary conserved danger control programs for tissue pathology. These programs date back to the survival benefits of the first multicellular organisms upon traumatic injuries by launching a series of danger control responses, i.e., 1. Haemostasis, or clotting to control bleeding; 2. Host defense, to control pathogen entry and spreading; 3. Re-epithelialisation, to recover barrier functions; and 4. Mesenchymal, to repair to regain tissue stability. Taking kidney pathology as an example, we discuss how clotting, inflammation, epithelial healing, and fibrosis/sclerosis determine the spectrum of kidney pathology, especially when they are insufficiently activated or present in an overshooting and deregulated manner. Understanding the evolutionary benefits of these response programs may refine the search for novel therapeutic targets to limit organ dysfunction in acute injuries and in progressive chronic tissue remodeling

Danger control programs cause tissue injury and remodeling.

Are there common pathways underlying the broad spectrum of tissue pathologies that develop upon injuries and from subsequent tissue remodeling? Here, we explain the pathophysiological impact of a set of evolutionary conserved danger control programs for tissue pathology. These programs date back to the survival benefits of the first multicellular organisms upon traumatic injuries by launching a series of danger control responses, i.e., 1. Haemostasis, or clotting to control bleeding; 2. Host defense, to control pathogen entry and spreading; 3. Re-epithelialisation, to recover barrier functions; and 4. Mesenchymal, to repair to regain tissue stability. Taking kidney pathology as an example, we discuss how clotting, inflammation, epithelial healing, and fibrosis/sclerosis determine the spectrum of kidney pathology, especially when they are insufficiently activated or present in an overshooting and deregulated manner. Understanding the evolutionary benefits of these response programs may refine the search for novel therapeutic targets to limit organ dysfunction in acute injuries and in progressive chronic tissue remodeling

Impact of an Interleukin-1 Receptor Antagonist and Erythropoietin on Experimental Myocardial Ischemia/Reperfusion Injury

Background. Revascularization of infarcted myocardium results in release of inflammatory cytokines mediating myocardial reperfusion injury and heart failure. Blockage of inflammatory pathways dampens myocardial injury and reduces infarct size. We compared the impact of the interleukin-1 receptor antagonist Anakinra and erythropoietin on myocardial ischemia/reperfusion injury. In contrast to others, we hypothesized that drug administration prior to reperfusion reduces myocardial damage. Methods and Results. 12–15 week-old Lewis rats were subjected to myocardial ischemia by a 1 hr occlusion of the left anterior descending coronary artery. After 15 min of ischemia, a single shot of Anakinra (2 mg/kg body weight (bw)) or erythropoietin (5000 IE/kg bw) was administered intravenously. In contrast to erythropoietin, Anakinra decreased infarct size (P < 0.05, N = 4/group) and troponin T levels (P < 0.05, N = 4/group). Conclusion. One-time intravenous administration of Anakinra prior to myocardial reperfusion reduces infarct size in experimental ischemia/reperfusion injury. Thus, Anakinra may represent a treatment option in myocardial infarction prior to revascularization

Do Attentional Lapses Account for the Worst Performance Rule?

The worst performance rule (WPR) describes the phenomenon that individuals’ slowest responses in a task are often more predictive of their intelligence than their fastest or average responses. To explain this phenomenon, it was previously suggested that occasional lapses of attention during task completion might be associated with particularly slow reaction times. Because less intelligent individuals should experience lapses of attention more frequently, reaction time distribution should be more heavily skewed for them than for more intelligent people. Consequently, the correlation between intelligence and reaction times should increase from the lowest to the highest quantile of the response time distribution. This attentional lapses account has some intuitive appeal, but has not yet been tested empirically. Using a hierarchical modeling approach, we investigated whether the WPR pattern would disappear when including different behavioral, self-report, and neural measurements of attentional lapses as predictors. In a sample of N = 85, we found that attentional lapses accounted for the WPR, but effect sizes of single covariates were mostly small to very small. We replicated these results in a reanalysis of a much larger previously published data set. Our findings render empirical support to the attentional lapses account of the WPR

Presentation of airway and general symptoms in COVID-19 caused by dominant SARS-CoV-2 variants : A follow-up on ARIA consensus

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