Mechanisms of transient nitric oxide and nitrous oxide production in a complex biofilm

Nitric oxide (NO) and nitrous oxide (N2O) are formed during N-cycling in complex microbial communities in response to fluctuating molecular oxygen (O2) and nitrite (NO2−) concentrations. Until now, the formation of NO and N2O in microbial communities has been measured with low spatial and temporal resolution, which hampered elucidation of the turnover pathways and their regulation. In this study, we combined microsensor measurements with metabolic modeling to investigate the functional response of a complex biofilm with nitrifying and denitrifying activity to variations in O2 and NO2−. In steady state, NO and N2O formation was detected if ammonium (NH4+) was present under oxic conditions and if NO2− was present under anoxic conditions. Thus, NO and N2O are produced by ammonia-oxidizing bacteria (AOB) under oxic conditions and by heterotrophic denitrifiers under anoxic conditions. NO and N2O formation by AOB occurred at fully oxic conditions if NO2− concentrations were high. Modeling showed that steady-state NO concentrations are controlled by the affinity of NO-consuming processes to NO. Transient accumulation of NO and N2O occurred upon O2 removal from, or NO2− addition to, the medium only if NH4+ was present under oxic conditions or if NO2− was already present under anoxic conditions. This showed that AOB and heterotrophic denitrifiers need to be metabolically active to respond with instantaneous NO and N2O production upon perturbations. Transiently accumulated NO and N2O decreased rapidly after their formation, indicating a direct effect of NO on the metabolism. By fitting model results to measurements, the kinetic relationships in the model were extended with dynamic parameters to predict transient NO release from perturbed ecosystems

2.45 GHz Passive Wireless Temperature Monitoring System Featuring Parallel Sensor Interrogation and Resolution Evaluation

IEEE SENSORS 2006, EXCO, Daegu, Korea / October 22-25, 200

Microdosing psychedelics: More questions than answers? An overview and suggestions for future research

Background: In the past few years, the issue of \u2018microdosing\u2019 psychedelics has been openly discussed in the public arena where claims have been made about their positive effect on mood state and cognitive processes such as concentration. However, there are very few scientific studies that have specifically addressed this issue, and there is no agreed scientific consensus on what microdosing is. Aim: This critique paper is designed to address questions that need to be answered by future scientific studies and to offer guidelines for these studies. Approach: Owing to its proximity for a possible approval in clinical use and short-lasting pharmacokinetics, our focus is predominantly on psilocybin. Psilocybin is allegedly, next to lysergic acid diethylamide (LSD), one of the two most frequently used psychedelics to microdose. Where relevant and available, data for other psychedelic drugs are also mentioned. Conclusion: It is concluded that while most anecdotal reports focus on the positive experiences with microdosing, future research should also focus on potential risks of (multiple) administrations of a psychedelic in low doses. To that end, (pre)clinical studies including biological (e.g. heart rate, receptor turnover and occupancy) as well as cognitive (e.g. memory, attention) parameters have to be conducted and will shed light on the potential negative consequences microdosing could have

Phase 1 Study of the E-Selectin Inhibitor GMI 1070 in Patients with Sickle Cell Anemia

Background\ud \ud Sickle cell anemia is an inherited disorder of hemoglobin that leads to a variety of acute and chronic complications. Abnormal cellular adhesion, mediated in part by selectins, has been implicated in the pathophysiology of the vaso-occlusion seen in sickle cell anemia, and selectin inhibition was able to restore blood flow in a mouse model of sickle cell disease.\ud \ud Methods\ud \ud We performed a Phase 1 study of the selectin inhibitor GMI 1070 in patients with sickle cell anemia. Fifteen patients who were clinically stable received GMI 1070 in two infusions.\ud \ud Results\ud \ud The drug was well tolerated without significant adverse events. There was a modest increase in total peripheral white blood cell count without clinical symptoms. Plasma concentrations were well-described by a two-compartment model with an elimination T1/2 of 7.7 hours and CLr of 19.6 mL/hour/kg. Computer-assisted intravital microscopy showed transient increases in red blood cell velocity in 3 of the 4 patients studied.\ud \ud Conclusions\ud \ud GMI 1070 was safe in stable patients with sickle cell anemia, and there was suggestion of increased blood flow in a subset of patients. At some time points between 4 and 48 hours after treatment with GMI 1070, there were significant decreases in biomarkers of endothelial activation (sE-selectin, sP-selectin, sICAM), leukocyte activation (MAC-1, LFA-1, PM aggregates) and the coagulation cascade (tissue factor, thrombin-antithrombin complexes). Development of GMI 1070 for the treatment of acute vaso-occlusive crisis is ongoing

Purple sulfur bacteria fix N-2 via molybdenum-nitrogenase in a low molybdenum Proterozoic ocean analogue

Biological N-2 fixation was key to the expansion of life on early Earth. The N-2-fixing microorganisms and the nitrogenase type used in the Proterozoic are unknown, although it has been proposed that the canonical molybdenum-nitrogenase was not used due to low molybdenum availability. We investigate N-2 fixation in Lake Cadagno, an analogue system to the sulfidic Proterozoic continental margins, using a combination of biogeochemical, molecular and single cell techniques. In Lake Cadagno, purple sulfur bacteria (PSB) are responsible for high N-2 fixation rates, to our knowledge providing the first direct evidence for PSB in situ N-2 fixation. Surprisingly, no alternative nitrogenases are detectable, and N-2 fixation is exclusively catalyzed by molybdenum-nitrogenase. Our results show that molybdenum-nitrogenase is functional at low molybdenum conditions in situ and that in contrast to previous beliefs, PSB may have driven N-2 fixation in the Proterozoic ocean. N-2 fixation was key to the expansion of life on Earth, but which organisms fixed N-2 and if Mo-nitrogenase was functional in the low Mo early ocean is unknown. Here, the authors show that purple sulfur bacteria fix N-2 using Mo-nitrogenase in a Proterozoic ocean analogue, despite low Mo conditions

Single cell analyses reveal contrasting life strategies of the two main nitrifiers in the ocean

Nitrification, the oxidation of ammonia via nitrite to nitrate, is a key process in marine nitrogen (N) cycling. Although oceanic ammonia and nitrite oxidation are balanced, ammonia-oxidizing archaea (AOA) vastly outnumber the main nitrite oxidizers, the bacterial Nitrospinae. The ecophysiological reasons for this discrepancy in abundance are unclear. Here, we compare substrate utilization and growth of Nitrospinae to AOA in the Gulf of Mexico. Based on our results, more than half of the Nitrospinae cellular N-demand is met by the organic-N compounds urea and cyanate, while AOA mainly assimilate ammonium. Nitrospinae have, under in situ conditions, around four-times higher biomass yield and five-times higher growth rates than AOA, despite their ten-fold lower abundance. Our combined results indicate that differences in mortality between Nitrospinae and AOA, rather than thermodynamics, biomass yield and cell size, determine the abundances of these main marine nitrifiers. Furthermore, there is no need to invoke yet undiscovered, abundant nitrite oxidizers to explain nitrification rates in the ocean

Parachute payments in English football: Softening the landing or distorting the balance?

This paper examines the impact of parachute payments in English league football in relation to the competitive balance of the second tier (the Championship). League results and parachute payment fees data were collected for the 11 seasons between 2006/07 and 2016/17. Overall competitive balance was analysed as well as specific aspects of competition that are fundamental to the league - promotion, survival and relegation. Our results show that an increase in the number of clubs with parachute payments and the overall value of these payments coincides with a reduction in competitive balance in the Championship. Furthermore, clubs with parachute payments are twice as likely to be promoted to the English Premier League and considerably less likely to suffer further relegation to the third tier (League 1). The paper therefore proposes either a re-distribution of parachute payments, the abolition of them completely, or a handicap points system to improve competitive balance