Crosstalk between ROS Homeostasis and Secondary Metabolism in S. natalensis ATCC 27448: Modulation of Pimaricin Production by Intracellular ROS

Streptomyces secondary metabolism is strongly affected by oxygen availability. The increased culture aeration enhances pimaricin production in S. natalensis, however the excess of O2 consumption can lead to an intracellular ROS imbalance that is harmful to the cell. The adaptive physiological response of S. natalensis upon the addition of exogenous H2O2 suggested that the modulation of the intracellular ROS levels, through the activation of the H2O2 inducible catalase during the late exponential growth phase, can alter the production of pimaricin. With the construction of defective mutants on the H2O2 related enzymes SodF, AhpCD and KatA1, an effective and enduring modulation of intracellular ROS was achieved. Characterization of the knock-out strains revealed different behaviours regarding pimaricin production: whilst the superoxide dismutase defective mutant presented low levels of pimaricin production compared to the wild-type, the mutants defective on the H2O2-detoxifying enzymes displayed a pimaricin overproducer phenotype. Using physiological and molecular approaches we report a crosstalk between oxidative stress and secondary metabolism regulatory networks. Our results reveal that the redox-based regulation network triggered by an imbalance of the intracellular ROS homeostasis is also able to modulate the biosynthesis of pimaricin in S. natalensis

Hypoglycemic episodes in hospitalized people with diabetes in Portugal: the HIPOS-WARD study

Background We intended to estimate the proportion hypoglycemic/hyperglycemic emergency episodes in treated diabetes mellitus (DM) patients admitted to a hospital ward, and calculate the prevalence of risk factors for hypoglycemia and diabetic complications. Methods In this cross-sectional, multicentered study, the observational data was collected by physicians from patient’s hospitalization to discharge/death. Statistical tests were 2-tailed considering 5% significance level. Results There were 646 ward admissions due to hyperglycemic emergencies and 176 hypoglycemic episodes with a ratio hypoglycemia/hyperglycemia 0.27 for all DM patients. In T2DM patients the ratio was 0.38. These were mainly female (55.1%), functionally dependent (61.4%) and retired/disabled (73.1%). Median age was 75 years and median duration of disease 11 years. Half the patients were on insulin-based therapy and 30.1% on secretagogue-based therapy. Approximately 57% of patients needed occasional/full assistance to manage the disease. The most frequent risk factor for hypoglycemia was polypharmacy (85.0%). Hypoglycemia in the 12 months before admission was higher in insulin-based therapy patients (66.1%; p = 0.001). Conclusions Hyperglycemic emergencies are the most frequent cause of hospitalization in Portugal, although severe hypoglycemic events represent a health and social problem in elderly/frail patients. There is still the need to optimize therapy in terms of the potential for hypoglycemia in this patient group and a review of anti-hyperglycemic agents to add on to insulin.info:eu-repo/semantics/publishedVersio

Responses of <i>Mytilus galloprovincialis</i> in a Multi-Stressor Scenario: Effects of an Invasive Seaweed Exudate and Microplastic Pollution under Ocean Warming

Microplastic pollution, global warming, and invasive species are known threats to marine biota, but the impact of their simultaneous exposure is still not well understood. This study investigated whether the toxic effects posed by the invasive red seaweed Asparagopsis armata exudate (2%) to the mussel Mytilus galloprovincialis are amplified by a 96 h exposure to increased temperature (24 °C) and polyethylene microplastics (PE-MPs, 1 mg/L). Biochemical (neurotoxicity, energy metabolism, oxidative stress, and damage) and physiological (byssal thread production) responses were evaluated. The number of produced byssus greatly decreased under concomitant exposure to all stressors. The antioxidant defences were depleted in the gills of mussels exposed to temperature rises and PE-MPs, regardless of exudate exposure, preventing oxidative damage. Moreover, the heat shock protein content tended to decrease in all treatments relative to the control. The increased total glutathione in the mussels’ digestive gland exposed to 24 °C, exudate, and PE-MPs avoided oxidative damage. Neurotoxicity was observed in the same treatment. In contrast, the energy metabolism remained unaltered. In conclusion, depending on the endpoint, simultaneous exposure to A. armata exudate, PE-MPs, and warming does not necessarily mean an amplification of their single effects. Studies focusing on the impact of multiple stressors are imperative to better understand the underlying mechanisms of this chronic exposure

How Does Mytilus galloprovincialis Respond When Exposed to the Gametophyte Phase of the Invasive Red Macroalga Asparagopsis armata Exudate?

Asparagopsis armata is classified as an invasive species in Europe. Through the exudation of secondary metabolites, this macroalga holds a chemical defence against consumers, with potential toxic effects to native rocky shore communities. This study aims to evaluate the potential impact of A. armata (gametophyte) exudate in a native species, the mussel Mytilus galloprovincialis, in terms of biochemical and organismal effects. The 96 h-LC50 was 3.667% and based on it, exudate concentrations (0.25; 0.5; 1; 2%) were determined to further sublethal experiments. These sublethal concentrations caused no oxidative damage in the digestive gland since lipid peroxidation and protein carbonylation were not affected. Nevertheless, there was a significant rise in the electron transport system activity and total glutathione content in muscle, suggesting an increased non-enzymatic antioxidant capacity and consequent energy consumption to cope with potential pro-oxidant compounds. This might have contributed to the observed decline in cellular energy allocation of the exposed mussels. At the organismal level, clearance capacity declined along the concentration gradient. Moreover, the number of functional byssuses decreased with increasing concentrations and a significant reduction in their attachment strength was observed. These findings suggest that the presence of A. armata may compromise M. galloprovincialis integrity in the invaded coastal areas

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved