Functional Molecular Diversity of Marine Dissolved Organic Matter Is Reduced during Degradation

Dissolved organic matter (DOM) is a highly diverse mixture of compounds, accounting for one of the world's largest active carbon pools. The surprising recalcitrance of some DOM compounds to bacterial degradation has recently been associated with its diversity. However, little is known about large-scale patterns of marine DOM diversity and its change through degradation, in particular considering the functional diversity of DOM. Here, we analyze the development of marine DOM diversity during degradation in two data sets comprising DOM of very different ages: a three-year mesocosm experiment and highly-resolved field samples from the Atlantic and Southern Ocean. The DOM molecular composition was determined using ultra-high resolution mass spectrometry. We quantify DOM diversity using three conceptually different diversity measures, namely richness of molecular formulas, abundance-based diversity, and functional molecular diversity. Using these measures we find stable molecular richness of DOM with age >1 year, systematic changes in the molecules' abundance distribution with degradation state, and increasing homogeneity with respect to chemical properties for more degraded DOM. Coinciding with differences in sea water density, the spatial field data separated clearly into regions of high and low diversity. The joint application of different diversity measures yields a comprehensive overview on temporal and spatial patterns of molecular diversity, valuable for general conclusions on drivers and consequences of marine DOM diversity

Functional molecular diversity of marine dissolved organic matter is reduced during degradation

Dissolved organic matter (DOM) is a highly diverse mixture of compounds, accounting for one of the world's largest active carbon pools. The surprising recalcitrance of some DOM compounds to bacterial degradation has recently been associated with its diversity. However, little is known about large-scale patterns of marine DOM diversity and its change through degradation, in particular considering the functional diversity of DOM. Here, we analyze the development of marine DOM diversity during degradation in two data sets comprising DOM of very different ages: a three-year mesocosm experiment and highly-resolved field samples from the Atlantic and Southern Ocean. The DOM molecular composition was determined using ultra-high resolution mass spectrometry. We quantify DOM diversity using three conceptually different diversity measures, namely richness of molecular formulas, abundance-based diversity, and functional molecular diversity. Using these measures we find stable molecular richness of DOM with age >1 year, systematic changes in the molecules' abundance distribution with degradation state, and increasing homogeneity with respect to chemical properties for more degraded DOM. Coinciding with differences in sea water density, the spatial field data separated clearly into regions of high and low diversity. The joint application of different diversity measures yields a comprehensive overview on temporal and spatial patterns of molecular diversity, valuable for general conclusions on drivers and consequences of marine DOM diversity

Disease- and sex-specific differences in patients with heart valve disease: a proteome study

Pressure overload in patients with aortic valve stenosis and volume overload in mitral valve regurgitation trigger specific forms of cardiac remodeling; however, little is known about similarities and differences in myocardial proteome regulation. We performed proteome profiling of 75 human left ventricular myocardial biopsies (aortic stenosis = 41, mitral regurgitation = 17, and controls = 17) using high-resolution tandem mass spectrometry next to clinical and hemodynamic parameter acquisition. In patients of both disease groups, proteins related to ECM and cytoskeleton were more abundant, whereas those related to energy metabolism and proteostasis were less abundant compared with controls. In addition, disease group-specific and sex-specific differences have been observed. Male patients with aortic stenosis showed more proteins related to fibrosis and less to energy metabolism, whereas female patients showed strong reduction in proteostasis-related proteins. Clinical imaging was in line with proteomic findings, showing elevation of fibrosis in both patient groups and sex differences. Disease- and sex-specific proteomic profiles provide insight into cardiac remodeling in patients with heart valve disease and might help improve the understanding of molecular mechanisms and the development of individualized treatment strategies

Old World megadroughts and pluvials during the Common Era

Climate model projections suggest widespread drying in the Mediterranean Basin and wetting in Fennoscandia in the coming decades largely as a consequence of greenhouse gas forcing of climate. To place these and other “Old World” climate projections into historical perspective based on more complete estimates of natural hydroclimatic variability, we have developed the “Old World Drought Atlas” (OWDA), a set of year-to-year maps of tree-ring reconstructed summer wetness and dryness over Europe and the Mediterranean Basin during the Common Era. The OWDA matches historical accounts of severe drought and wetness with a spatial completeness not previously available. In addition, megadroughts reconstructed over north-central Europe in the 11th and mid-15th centuries reinforce other evidence from North America and Asia that droughts were more severe, extensive, and prolonged over Northern Hemisphere land areas before the 20th century, with an inadequate understanding of their causes. The OWDA provides new data to determine the causes of Old World drought and wetness and attribute past climate variability to forced and/or internal variability

Metabolic Profiling as Well as Stable Isotope Assisted Metabolic and Proteomic Analysis of RAW 264.7 Macrophages Exposed to Ship Engine Aerosol Emissions: Different Effects of Heavy Fuel Oil and Refined Diesel Fuel

Exposure to air pollution resulting from fossil fuel combustion has been linked to multiple short-term and long term health effects. In a previous study, exposure of lung epithelial cells to engine exhaust from heavy fuel oil (HFO) and diesel fuel (DF), two of the main fuels used in marine engines, led to an increased regulation of several pathways associated with adverse cellular effects, including pro-inflammatory pathways. In addition, DF exhaust exposure was shown to have a wider response on multiple cellular regulatory levels compared to HFO emissions, suggesting a potentially higher toxicity of DF emissions over HFO. In order to further understand these effects, as well as to validate these findings in another cell line, we investigated macrophages under the same conditions as a more inflammationrelevant model. An air-liquid interface aerosol exposure system was used to provide a more biologically relevant exposure system compared to submerged experiments, with cells exposed to either the complete aerosol (particle and gas phase), or the gas phase only (with particles filtered out). Data from cytotoxicity assays were integrated with metabolomics and proteomics analyses, including stable isotope-assisted metabolomics, in order to uncover pathways affected by combustion aerosol exposure in macrophages. Through this approach, we determined differing phenotypic effects associated with the different components of aerosol. The particle phase of diluted combustion aerosols was found to induce increased cell death in macrophages, while the gas phase was found more to affect the metabolic profile. In particular, a higher cytotoxicity of DF aerosol emission was observed in relation to the HFO aerosol. Furthermore, macrophage exposure to the gas phase of HFO leads to an induction of a pro-inflammatory metabolic and proteomic phenotype. These results validate the effects found in lung epithelial cells, confirming the role of inflammation and cellular stress in the response to combustion aerosols

Eigenständige Analgesie mit Piritramid durch Notfallsanitäter – retrospektive Auswertung der elektronischen Einsatzdokumentation

Hintergrund Schmerzen sind ein häufiger Behandlungsgrund in der prähospitalen Notfallmedizin. In Bayern delegieren die Ärztlichen Leiter Rettungsdienst (ÄLRD) bei subjektiv nichttolerablen Schmerzen nach isoliertem Extremitätentrauma an Notfallsanitäter (NotSan) landesweit einheitlich die Kurzinfusion von 7,5 mg des Opioidanalgetikums Piritramid. Methode Die Routineeinsatzdokumentation aller Einsätze im bayerischen Rettungsdienst mit Heranziehungen des Delegationsalgorithmus „Isolierte Extremitätenverletzung“ der ÄLRD nach § 4 Abs. 2 Nr. 2c Notfallsanitätergesetz wurde über einen 2‑Jahres-Zeitraum ausgewertet. Evaluiert wurden der Effekt auf die Schmerzintensität nach der numerischen Rating-Skala (NRS) und dem Vorliegen nichttolerabler Schmerzen, Auswirkungen auf die Vitalfunktionen sowie die Notwendigkeit von bestimmten weitergehenden Interventionen. Ergebnisse Bei 7151 identifizierten Einsätzen erfolgte in 6097 Fällen eine eigenständige Analgesie durch NotSan entlang der Delegation der ÄLRD. Die Schmerzintensität nach der NRS konnte von im Median 7 (Interquartilsabstand [IQR] 2) auf 3 (IQR 2, p < 0,001) gesenkt und in 96,9 % ein aus Patientensicht tolerables Niveau erreicht werden. In 9,4 % der Fälle wurde ein Notarzt nachgefordert und in 5,0 % eine ergänzende Analgesie verabreicht. Etwa jeder zehnte Patient erhielt Sauerstoff. Atemwegsinterventionen waren in wenigen Einzelfällen notwendig, eine Antagonisierung nur nach höheren als den delegierten Opiatdosen. Schlussfolgerung Eine vom ÄLRD delegierte und von NotSan eigenständig durchgeführte Opiatgabe senkt das Schmerzniveau relevant. Wesentliche Hinweise auf eine Patientengefährdung fanden sich nicht. Durch dieses Verfahren konnten in Bayern jährlich geschätzt ca. 2500 Notarzteinsätze vermieden werden

Identification of Ischemic Regions in a Rat Model of Stroke

Investigations following stroke first of all require information about the spatio-temporal dimension of the ischemic core as well as of perilesional and remote affected tissue. Here we systematically evaluated regions differently impaired by focal ischemia.Wistar rats underwent a transient 30 or 120 min suture-occlusion of the middle cerebral artery (MCAO) followed by various reperfusion times (2 h, 1 d, 7 d, 30 d) or a permanent MCAO (1 d survival). Brains were characterized by TTC, thionine, and immunohistochemistry using MAP2, HSP72, and HSP27. TTC staining reliably identifies the infarct core at 1 d of reperfusion after 30 min MCAO and at all investigated times following 120 min and permanent MCAO. Nissl histology denotes the infarct core from 2 h up to 30 d after transient as well as permanent MCAO. Absent and attenuated MAP2 staining clearly identifies the infarct core and perilesional affected regions at all investigated times, respectively. HSP72 denotes perilesional areas in a limited post-ischemic time (1 d). HSP27 detects perilesional and remote impaired tissue from post-ischemic day 1 on. Furthermore a simultaneous expression of HSP72 and HSP27 in perilesional neurons was revealed.TTC and Nissl staining can be applied to designate the infarct core. MAP2, HSP72, and HSP27 are excellent markers not only to identify perilesional and remote areas but also to discriminate affected neuronal and glial populations. Moreover markers vary in their confinement to different reperfusion times. The extent and consistency of infarcts increase with prolonged occlusion of the MCA. Therefore interindividual infarct dimension should be precisely assessed by the combined use of different markers as described in this study

Rodent models of focal cerebral ischemia: procedural pitfalls and translational problems

Rodent models of focal cerebral ischemia are essential tools in experimental stroke research. They have added tremendously to our understanding of injury mechanisms in stroke and have helped to identify potential therapeutic targets. A plethora of substances, however, in particular an overwhelming number of putative neuroprotective agents, have been shown to be effective in preclinical stroke research, but have failed in clinical trials. A lot of factors may have contributed to this failure of translation from bench to bedside. Often, deficits in the quality of experimental stroke research seem to be involved. In this article, we review the commonest rodent models of focal cerebral ischemia - middle cerebral artery occlusion, photothrombosis, and embolic stroke models - with their respective advantages and problems, and we address the issue of quality in preclinical stroke modeling as well as potential reasons for translational failure