Cascading events during the 1650 tsunamigenic eruption of Kolumbo volcano.

Volcanic eruptions can trigger tsunamis, which may cause significant damage to coastal communities and infrastructure. Tsunami generation during volcanic eruptions is complex and often due to a combination of processes. The 1650 eruption of the Kolumbo submarine volcano triggered a tsunami causing major destruction on surrounding islands in the Aegean Sea. However, the source mechanisms behind the tsunami have been disputed due to difficulties in sampling and imaging submarine volcanoes. Here we show, based on three-dimensional seismic data, that ~1.2 km³ of Kolumbo's northwestern flank moved 500-1000 m downslope along a basal detachment surface. This movement is consistent with depressurization of the magma feeding system, causing a catastrophic explosion. Numerical tsunami simulations indicate that only the combination of flank movement followed by an explosive eruption can explain historical eyewitness accounts. This cascading sequence of natural hazards suggests that assessing submarine flank movements is critical for early warning of volcanogenic tsunamis.

Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination.

We report findings in five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against coronavirus disease 2019 (Covid-19). The patients were health care workers who were 32 to 54 years of age. All the patients had high levels of antibodies to platelet factor 4-polyanion complexes; however, they had had no previous exposure to heparin. Because the five cases occurred in a population of more than 130,000 vaccinated persons, we propose that they represent a rare vaccine-related variant of spontaneous heparin-induced thrombocytopenia that we refer to as vaccine-induced immune thrombotic thrombocytopenia.

Phenotypic plasticity of coralline algae in a High CO2 world.

It is important to understand how marine calcifying organisms may acclimatize to ocean acidification to assess their survival over the coming century. We cultured the cold water coralline algae, Lithothamnion glaciale, under elevated pCO2 (408, 566, 770, and 1024 µatm) for 10 months. The results show that the cell (inter and intra) wall thickness is maintained, but there is a reduction in growth rate (linear extension) at all elevated pCO2. Furthermore a decrease in Mg content at the two highest CO2 treatments was observed. Comparison between our data and that at 3 months from the same long-term experiment shows that the acclimation differs over time since at 3 months, the samples cultured under high pCO2 showed a reduction in the cell (inter and intra) wall thickness but a maintained growth rate. This suggests a reallocation of the energy budget between 3 and 10 months and highlights the high degree plasticity that is present. This might provide a selective advantage in future high CO2 world.

Chiral N-benzyl-N-methyl-1-(naphthalen-1-yl)ethanamines and their in vitro antifungal activity against Cryptococcus neoformans, Trichophyton mentagrophytes and Trichophyton rubrum.

In the search for new antifungal compounds and to explore structure activity relationships, a series of 24 chiral benzyl amine type antifungals was synthesised and characterised. In vitro testing against the human pathogen Cryptococcus neoformans revealed that several derivatives had MIC50 values similar to that of the commercial drug Butenafine. All of these contained a bulky group in the para position of the benzyl fragment. Eighteen compounds were also tested for activity against the dermatophytes Trichophyton mentagrophytes and Trichophyton rubrum. Of these (R)-N-(4-tert-butylbenzyl)-N-methyl-1-(naphthalen-1-yl)ethanamine (MIC50: 0.06 µg/mL) and a para-benzyloxy substituted derivative (MIC50: 0.125 µg/mL) possessed high activity. Testing of derivatives with a stereocentre at the benzylic carbon, revealed that (S)-stereochemistry was required for potency: a MIC50 value of 1 µg/mL was obtained for (S)-1-(4-tert-butylphenyl)-N-methyl-N-(naphthalen-1-ylmethyl)ethanamine. Preparation of the corresponding fluoromethyl compound was achieved employing lipase B from Candida antarctica as catalyst in the key step. A low antifungal activity was observed for the fluorinated derivative indicating the importance of the amine basicity for the antifungal potency of these compounds.

Genetic variability and structure of the water vole Arvicola amphibius across four metapopulations in northern Norway.

Water vole Arvicola amphibius populations have recently experienced severe decline in several European countries as a consequence of both reduction in suitable habitat and the establishment of the alien predator American mink Neovison vison. We used DNA microsatellite markers to describe the genetic structure of 14 island populations of water vole off the coast of northern Norway. We looked at intra- and inter-population levels of genetic variation and examined the effect of distance among pairs of populations on genetic differentiation (isolation by distance). We found a high level of genetic differentiation (measured by F ST) among populations overall as well as between all pairs of populations. The genetic differentiation between populations was positively correlated with geographic distance between them. A clustering analysis grouped individuals into 7 distinct clusters and showed the presence of 3 immigrants among them. Our results suggest a small geographic scale for evolutionary and population dynamic processes in our water vole populations.

Evidence of inbreeding depression but not inbreeding avoidance in a natural house sparrow population.

Inbreeding is common in small and threatened populations and often has a negative effect on individual fitness and genetic diversity. Thus, inbreeding can be an important factor affecting the persistence of small populations. In this study, we investigated the effects of inbreeding on fitness in a small, wild population of house sparrows (Passer domesticus) on the island of Aldra, Norway. The population was founded in 1998 by four individuals (one female and three males). After the founder event, the adult population rapidly increased to about 30 individuals in 2001. At the same time, the mean inbreeding coefficient among adults increased from 0 to 0.04 by 2001 and thereafter fluctuated between 0.06 and 0.10, indicating a highly inbred population. We found a negative effect of inbreeding on lifetime reproductive success, which seemed to be mainly due to an effect of inbreeding on annual reproductive success. This resulted in selection against inbred females. However, the negative effect of inbreeding was less strong in males, suggesting that selection against inbred individuals is at least partly sex specific. To examine whether individuals avoided breeding with close relatives, we compared observed inbreeding and kinship coefficients in the population with those obtained from simulations of random mating. We found no significant differences between the two, indicating weak or absent inbreeding avoidance. We conclude that there was inbreeding depression in our population. Despite this, birds did not seem to actively avoid mating with close relatives, perhaps as a consequence of constraints on mating possibilities in such a small population.

Ocean acidification weakens the structural integrity of coralline algae.

The uptake of anthropogenic emission of carbon dioxide is resulting in a lowering of the carbonate saturation state and a drop in ocean pH. Understanding how marine calcifying organisms such as coralline algae may acclimatize to ocean acidification is important to understand their survival over the coming century. We present the first long-term perturbation experiment on the cold-water coralline algae, which are important marine calcifiers in the benthic ecosystems particularly at the higher latitudes. Lithothamnion glaciale, after three months incubation, continued to calcify even in undersaturated conditions with a significant trend towards lower growth rates with increasing pCO2 . However, the major changes in the ultra-structure occur by 589 µatm (i.e. in saturated waters). Finite element models of the algae grown at these heightened levels show an increase in the total strain energy of nearly an order of magnitude and an uneven distribution of the stress inside the skeleton when subjected to similar loads as algae grown at ambient levels. This weakening of the structure is likely to reduce the ability of the alga to resist boring by predators and wave energy with severe consequences to the benthic community structure in the immediate future (50 years).

Quality control of metoprolol extended-release formulations in the presence of ethanol.

This paper presents in-vitro metoprolol release from four different extended-release (ER) formulations, i.e. Metoprolol GEA® Retard, Logimax® forte, Metoprolol Sandoz® and Seloken ZOC® in the presence of 10 to 40% (v/v%) ethanol at pH 1.2 and pH 6.8. The assay of metoprolol in the dissolution media was performed by reversed phase liquid chromatography (RP-LC) using a mixture of methanol and 100 mM phosphate buffer (pH 3.5) in 40:60 ratio as eluent. The dissolution data showed that the metoprolol contents of Metoprolol Sandoz® and Seloken ZOC® were released fast in the presence of 20% ethanol at the investigated conditions, while the other products demonstrated much more stability against ethanol. Unexpectedly it was discovered that the release of metoprolol from Metoprolol GEA® Retard and to some extent also from Logimax® forte decreased in the ethanol containing media.

Sex-specific fitness correlates of dispersal in a house sparrow metapopulation.

1. Dispersal affects many important ecological and evolutionary processes. Still, little is known about the fitness of dispersing individuals. 2. Here, we use data from a long-term study of a house sparrow Passer domesticus metapopulation to compare lifetime reproductive success (LRS) of resident and immigrant individuals, all with known origin. 3. Lifetime production of recruits by immigrant males was much lower than for resident males, because of shorter life span and lower annual mating success. In contrast, lifetime production of recruits did not differ significantly between immigrant and resident females. 4. Over their lifetime, dispersers contributed fewer recruits to the local population than residents. This shows that immigrant house sparrows have different, sex specific, demographic effects on the population dynamics than residents.

The origin of stable halogenated compounds in volcanic gases.

BACKGROUND: Halogenated compounds in the atmosphere are of great environmental concern due to their demonstrated negative effect on atmospheric chemistry and climate. Detailed knowledge of the emission budgets of halogenated compounds has to be gained to understand better their specific impact on ozone chemistry and the climate. Such data are also highly relevant to guide policy decisions in connexion with international agreements about protection of the ozone layer. In selected cases, the relevance of specific emission sources for certain compounds were unclear. In this study we present new and comprehensive evidence regarding the existence and relevance of a volcanic contribution of chlorofluorocarbons (CFCs), hydrofluorocarbons (HFCs), hydrochlorofluorocarbons (HCFCs), halons (bromine containing halo(hydro)carbons), and fully fluorinated compounds (e.g. CF4 and SF6) to the atmospheric budget. METHODS: In order to obtain new evidence of a volcanic origin of these compounds, we collected repeatedly, during four field campaigns covering a period of two years, gases from fumaroles discharging over a wide range of temperatures at the Nicaraguan subduction zone volcanoes Momotombo, Cerro Negro and Mombacho, and analysed them with very sensitive GC/MS systems. RESULTS AND DISCUSSION: In most fumarolic samples certain CFCs, HFCs, HCFCs, halons, and the fully fluorinated compounds CF4 and SF6 were present above detection limits. However, these compounds occur in the fumarole gases in relative proportions characteristic for ambient air. CONCLUSION: This atmospheric fingerprint can be explained by variable amounts of air entering the porous volcanic edifices and successively being incorporated into the fumarolic gas discharges. Recommendation and Outlook. Our results suggest that the investigated volcanoes do not constitute a significant natural source for CFCs, HFCs, HCFCs, halons, CF4, SF6 and NF3.

Intracellular Ca2+ chelators prevent DNA damage and protect hepatoma 1C1C7 cells from quinone-induced cell killing.

Exposure of hepatoma 1c1c7 cells to 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) resulted in a sustained elevation of cytosolic Ca2+, DNA single strand breaks and cell killing. DNA single strand break formation was prevented when cells were preloaded with either of the intracellular Ca2+ chelators, Quin 2 or BAPTA, to buffer the increase in cytosolic Ca2+ concentration induced by the quinone. DMNQ caused marked NAD+ depletion which was prevented when cells were preincubated with 3-aminobenzamide, an inhibitor of nuclear poly-(ADP-ribose)-synthetase activity, or with either of the two Ca2+ chelators. However, 3-aminobenzamide did not protect the hepatoma cells from loss of viability. Our results indicate that quinone-induced DNA damage, NAD+ depletion and cell killing are mediated by a sustained elevation of cytosolic Ca2+.

Cytoskeletal alterations in human platelets exposed to oxidative stress are mediated by oxidative and Ca2+-dependent mechanisms.

The metabolism of the redox-active quinone, menadione (2-methyl-1,4-naphthoquinone), in human platelets was associated with superoxide anion production, oxidation and depletion of intracellular glutathione, and modification of protein thiols. The cytoskeletal fraction extracted from menadione-treated platelets exhibited a dose-dependent increase in the amount of cytoskeleton-associated protein and a concomitant loss of protein thiols. These alterations were associated with oxidative modifications of actin, including beta-mercaptoethanol-sensitive crosslinking of actin to form dimers, trimers, and high-molecular-weight aggregates which also contained other cytoskeletal proteins, i.e., alpha-actinin and actin-binding protein. In addition, analysis of the cytoskeletal fraction from platelets treated with high concentrations (greater than or equal to 100 microM) of menadione by polyacrylamide gel electrophoresis under reducing conditions revealed a net decrease in the relative abundance of the individual cytoskeletal polypeptides. Under the same incubation conditions the platelets exhibited a sustained increase in cytosolic Ca2+ concentration. The presence of glucose, or the omission of Ca2+ from the incubation medium, prevented both the increase in cytosolic Ca2+ and the decrease in the relative amounts of cytoskeletal proteins. The latter effect was also largely prevented in platelets loaded with Quin-2 tetraacetoxymethyl ester to buffer the menadione-induced elevation of cytosolic Ca2+. Finally, the presence of a protease inhibitor, leupeptin, in the incubation medium prevented the menadione-induced decrease in the amount of actin-binding protein but not the decrease in the other cytoskeletal proteins. Our findings demonstrate that the multiple effects of oxidative stress on the platelet cytoskeleton are mediated by oxidative as well as by Ca2+-dependent mechanisms.

Detection of oxygen radicals during reperfusion of intestinal cells in vitro.

The nitroxide OXANO. (2-Ethyl-2,5,5-trimethyl-3-oxazolidinoxyl) which in its reduced form, OXANOH (2-Ethyl-1-hydroxy-2,5,5-trimethyl-3-oxazolidine), is capable of reacting with short-lived radicals, forming a secondary stable radical, was used for ESR-detection of radical production in isolated cells. The properties of OXANO. and OXANOH in terms of stability in cellular and subcellular systems, membrane permeability and effects on cellular viability were evaluated. Ischemia and reperfusion was simulated in vitro in a preparation of cells from rat intestinal mucosa by incubation at high density (4 X 10(8) cells/ml) under an atmosphere of nitrogen for 25 min and resuspended with fresh oxygenated buffer containing 5 mM OXANOH. A significant increase in radical formation during the 15 min reperfusion period studied was obtained in cells exposed to ischemia compared to control cells incubated at normal density under an atmosphere of oxygen. The addition of 5 microM of the scavenging enzyme superoxide dismutase reduced the radical formation by 50%. The time sequence of the superoxide formation was calculated as the difference in radical production in the presence and absence of superoxide dismutase.

Cytosolic-free Ca2+ and cell killing in hepatoma 1c1c7 cells exposed to chemical anoxia.

Exposure of cultured hepatoma 1c1c7 cells to KCN and iodoacetate, to produce chemical anoxia, caused a rapid and sustained increase in cytosolic-free Ca2+ concentration, which was associated with depletion of intracellular ATP and glutathione. These changes occurred before the loss of cell viability and were accompanied by the appearance of plasma membrane blebs. Pretreatment of the cells with the Ca2+ chelators Quin 2 or BAPTA markedly delayed both the onset of blebbing and loss of cell viability, but did not affect KCN- and iodoacetate-induced loss of ATP and glutathione. Together, these results strongly suggest that a sustained increase in cytosolic Ca2+ concentration plays an important role in killing of hepatoma cells by chemical anoxia.

Alterations in hepatocyte cytoskeleton caused by redox cycling and alkylating quinones.

Quinones may induce toxicity by a number of mechanisms, including alkylation and oxidative stress following redox cycling. The metabolism of quinones by isolated rat hepatocytes is associated with cytoskeletal alterations, plasma membrane blebbing, and subsequent cytotoxicity. The different mechanisms underlying the effects of alkylating (p-benzoquinone), redox cycling (2,3-dimethoxy-1,4-naphthoquinone), and mixed redox cycling/alkylating (2-methyl-1,4-naphthoquinone) quinones on hepatocyte cytoskeleton have been investigated in detail in this study. Analysis of the cytoskeletal fraction extracted from quinone-treated cells revealed a concentration-dependent increase in the amount of cytoskeletal protein and a concomitant loss of protein thiols, irrespective of the quinone employed. In the case of redox cycling quinones, these alterations were associated with an oxidation-dependent actin crosslinking (sensitive to the thiol reductant dithiothreitol). In contrast, with alkylating quinones an oxidation-independent cytoskeletal protein crosslinking (insensitive to thiol reductants) was observed. In addition to these changes, a dose-dependent increase in the relative abundance of F-actin was detected as a consequence of the metabolism of oxidizing quinones in hepatocytes. Addition of dithiothreitol solubilized a considerable amount of polypeptides from the cytoskeletal fraction isolated from hepatocytes exposed to redox cycling but not alkylating quinones. Our findings indicate that the hepatocyte cytoskeleton is an important target for the toxic effects of different quinones. However, the mechanisms underlying cytoskeletal damage differ depending on whether the quinone acts primarily by oxidative stress or alkylation.

Menadione-induced bleb formation in hepatocytes is associated with the oxidation of thiol groups in actin.

Incubation of isolated rat hepatocytes with menadione (2-methyl-1,4-naphthoquinone) or the thiol oxidant, diamide (azodicarboxylic acid bis(dimethylamide)), resulted in the appearance of numerous plasma membrane protrusions (blebs) preceding cell death. Analysis of the Triton X-100-insoluble fraction (cytoskeleton) extracted from treated cells revealed a dose- and time-dependent increase in the amount of cytoskeletal protein and a concomitant loss of protein thiols. These changes were associated with the disappearance of actin and formation of large-molecular-weight aggregates, when the cytoskeletal proteins were analyzed by polyacrylamide gel electrophoresis under nonreducing conditions. However, if the cytoskeletal proteins were treated with the thiol reductants, dithiothreitol or beta-mercaptoethanol, no changes in the relative abundance of actin or formation of large-molecular-weight aggregates were detected in the cytoskeletal preparations from treated cells. Moreover, addition of dithiothreitol to menadione- or diamide-treated hepatocytes protected the cells from both the appearance of surface blebs and the occurrence of alterations in cytoskeletal protein composition. Our findings show that oxidative stress induced by the metabolism of menadione in isolated hepatocytes causes cytoskeletal abnormalities, of which protein thiol oxidation seems to be intimately related to the appearance of surface blebs.

Cellular metabolism of arsenocholine.

The biotransformation of arsenocholine and arsenobetaine, which are organic arsenic compounds present in certain aquatic organisms, has been studied in vitro using synthetic reference substances. Incubation of arsenocholine with different liver cell fractions showed arsenocholine to be biotransformed only in presence of the mitochondrial fraction. The biotransformation products were arsenobetaine aldehyde, arsenobetaine, trimethylarsine oxide and trimethylarsine. Arsenobetaine was the major metabolite and it was formed via arsenobetaine aldehyde. Trimethylarsine oxide was formed via a side reaction from arsenobetaine aldehyde. Further reduction of trimethylarsine oxide, produced trimethylarsine. In vitro studies of arsenobetaine, did not show any formation of trimethylarsine oxide or trimethylarsine. Furthermore, cytotoxicity of arsenobetaine or arsenocholine in isolated hepatocytes was not observed.