Eruptive history of the Late Quaternary Ciomadul (Csomád) volcano, East Carpathians, part II: magma output rates

This study, which builds on high-precision unspiked Cassignol-Gillot K-Ar age determinations, presents an advanced DEMbased volumetrical analysis to infer long-term magma output rates for the Late Quaternary Ciomadul (Csomád) dacitic lava dome complex (East Carpathians, Romania). The volcanic field of Ciomadul developed on the erosional surface of Lower Cretaceous flysch and ~ 2 Ma old andesites and experienced an extended eruptive history from ~ 850 to < 30 ka. Predominantly effusive activity took place during the first stage (~ 850 to ~ 440 ka), producing volumetrically minor, isolated, peripheral domes. Subsequently, after a ~ 250 ky repose interval, a voluminous central dome cluster developed in the second stage (~ 200 to < 30 ka). During the youngest phase of evolution (~ 60 to < 30 ka), highly explosive eruptions also occurred, resulting in the formation of two craters (Mohos and St. Ana). The calculated ~ 8.00 ± 0.55 km3 total volume of the lava domes, which includes the related volcaniclastic (1.57 km3 ) as well as erosionally removed (0.18 km3 ) material, is in line with dimensions of other medium-sized dacitic lava domes worldwide. This volume was extruded at an average long-term magma output rate of 9.76 km3 / My (0.0098 km3 /ky). However, most of the domes (7.53 ± 0.51 km3 ) were formed in the 200 to < 30 ka period, implying a significantly increased magma output rate of 37.40 km3 /My (0.0374 km3 /ky), more than 30 times higher than in the first stage. Within these long-term trends, individual lava domes of Ciomadul (e.g. those with volumes between 0.02 and 0.40 km3 ) would have been emplaced at much higher rates over a period of years to tens of years. The active periods, lasting up to hundreds of years, would have been followed by repose periods ~ 30 times longer. The most recent eruption of Ciomadul has been dated here at 27.7 ± 1.4 ka. This age, which is in agreement with radiocarbon dates for the onset of lake sediment accumulation in St. Ana crater, dates fragmented lava blocks which are possibly related to a disrupted dome. This suggests that during the last, typically explosive, phase of Ciomadul, lava dome extrusion was still ongoing. In a global context, the analysis of the volumetric dynamism of Ciomadul’s activity gives insights into the temporal variations in magma output; at lava domes, short-term (dayor week-scale) eruption rates smooth out in long-term (millenia-scale) output rates which are tens of times lower

Acquired nintedanib resistance in FGFR1-driven small cell lung cancer: Role of endothelin-A receptor-activated ABCB1 expression

Genomically amplified fibroblast growth factor receptor 1 (FGFR1) is an oncogenic driver in defined lung cancer subgroups and predicts sensibility against FGFR1 inhibitors in this patient cohort. The FGFR inhibitor nintedanib has recently been approved for treatment of lung adenocarcinoma and is currently evaluated for small cell lung cancer (SCLC). However, tumor recurrence due to development of nintedanib resistance might occur. Hence, we aimed at characterizing the molecular mechanisms underlying acquired nintedanib resistance in FGFR1-driven lung cancer. Chronic nintedanib exposure of the FGFR1-driven SCLC cell line DMS114 (DMS114/ NIN) but not of two NSCLC cell lines induced massive overexpression of the multidrug-resistance transporter ABCB1. Indeed, we proved nintedanib to be both substrate and modulator of ABCB1-mediated efflux. Importantly, the oncogenic FGFR1 signaling axis remained active in DMS114/NIN cells while bioinformatic analyses suggested hyperactivation of the endothelin-A receptor (ETAR) signaling axis. Indeed, ETAR inhibition resensitized DMS114/NIN cells against nintedanib by downregulation of ABCB1 expression. PKC and downstream NFκB were identified as major downstream players in ETAR-mediated ABCB1 hyperactivation. Summarizing, ABCB1 needs to be considered as a factor underlying nintedanib resistance. Combination approaches with ETAR antagonists or switching to non-ABCB1 substrate FGFR inhibitors represent innovative strategies to manage nintedanib resistance in lung cancer

Wheat-barley hybridization – the last forty years

Abstract Several useful alien gene transfers have been reported from related species into wheat (Triticum aestivum), but very few publications have dealt with the development of wheat/barley (Hordeum vulgare) introgression lines. An overview is given here of wheat 9 barley hybridization over the last forty years, including the development of wheat 9 barley hybrids, and of addition and translocation lines with various barley cultivars. A short summary is also given of the wheat 9 barley hybrids produced with other Hordeum species. The meiotic pairing behaviour of wheat 9 barley hybrids is presented, with special regard to the detection of wheat– barley homoeologous pairing using the molecular cytogenetic technique GISH. The effect of in vitro multiplication on the genome composition of intergeneric hybrids is discussed, and the production and characterization of the latest wheat/barley translocation lines are presented. An overview of the agronomical traits (b-glucan content, earliness, salt tolerance, sprouting resistance, etc.) of the newly developed introgression lines is given. The exploitation and possible use of wheat/barley introgression lines for the most up-to-date molecular genetic studies (transcriptome analysis, sequencing of flow-sorted chromosomes) are also discussed

Cytomolecular identification of individual wheat-wheat chromosome arm associations in wheat-rye hybrids

Chromosome pairing in the meiotic metaphase I of wheatrye hybrids has been characterized by sequential genomic and fluorescent in situ hybridization allowing not only the discrimination of wheat and rye chromosomes, but also the identification of the individual wheat and rye chromosome arms involved in the chromosome associations. The majority of associations (93.8%) were observed between the wheat chromosomes. The largest number of wheat-wheat chromosome associations (53%) was detected between the A and D genomes, while the frequency of B-D and A-B associations was significantly lower (32 and 8%, respectively). Among the A-D chromosome associations, pairing between the 3AL and 3DL arms was observed with the highest frequency, while the most frequent of all the chromosome associations (0.113/ cell) was found to be the 3DS-3BS. Differences in the pairing frequency of the individual chromosome arms of wheat-rye hybrids have been discussed in relation to the homoeologous relationships between the constituent genomes of hexaploid wheat

In vivo characterization of [18F]AVT-011 as a radiotracer for PET imaging of multidrug resistance

Multidrug resistance (MDR) impedes cancer treatment. Two efflux transporters from the ATP-binding cassette (ABC) family, ABCB1 and ABCG2, may contribute to MDR by restricting the entry of therapeutic drugs into tumor cells. Although a higher expression of these transporters has been correlated with an unfavorable response to chemotherapy, transporter expression does not necessarily correlate with function. In this study, we characterized the pharmacological properties of [18F]AVT-011, a new PET radiotracer for imaging transporter-mediated MDR in tumors.AVT-011 was radiolabeled with 18F and evaluated with PET imaging in preclinical models. Transport of [18F]AVT-011 by ABCB1 and/or ABCG2 was assessed by measuring its uptake in the brains of wild-type, Abcb1a/b-/-, and Abcg2-/- mice at baseline and after administration of the ABCB1 inhibitor tariquidar (n = 5/group). Metabolism and biodistribution of [18F]AVT-011 were also measured. To measure ABCB1 function in tumors, we performed PET experiments using both [18F]AVT-011 and [18F]FDG in mice bearing orthotopic breast tumors (n = 7-10/group) expressing clinically relevant levels of ABCB1.At baseline, brain uptake was highest in Abcb1a/b-/- mice. After tariquidar administration, brain uptake increased 3-fold and 8-fold in wild-type and Abcg2-/- mice, respectively, but did not increase further in Abcb1a/b-/- mice. At 30 min after injection, the radiotracer was > 90% in its parent form and had highest uptake in organs of the hepatobiliary system. Compared with that in drug-sensitive tumors, uptake of [18F]AVT-011 was 32% lower in doxorubicin-resistant tumors with highest ABCB1 expression and increased by 40% with tariquidar administration. Tumor uptake of [18F]FDG did not significantly differ among groups.[18F]AVT-011 is a dual ABCB1/ABCG2 substrate radiotracer that can quantify transporter function at the blood-brain barrier and in ABCB1-expressing tumors, making it potentially suitable for clinical imaging of ABCB1-mediated MDR in tumors

The link between lithospheric scale deformations and deep fluid emanations: Inferences from the Southeastern Carpathians, Romania

Understanding the formation, migration and emanation of deep CO2, H2O and noble gases (He–Ne) in deep-seated deformation settings is crucial to understand the complex relationship between deep-originated fluids and lithospheric deformation. To gain a better insight into these phenomena, we studied the origin of H2O, CO2 and noble gases of gas-rich springs found in the Târgu Secuiesc Basin located in the southeasternmost part of the Carpathian-Pannonian region of Europe. This study area is one of the best natural examples to understand the connection between the deep sources of gas emanations and deep-seated deformation zones, providing an excellent analogue for regions worldwide with similar tectonic settings and fluid emanation properties. We studied the δ2H and δ18O stable isotopic ratios of the spring waters, and the δ13C, He and Ne stable isotopic ratio of the emanating CO2-rich gases dissolved in the mineral spring waters in Covasna town and its vicinity. Based on the δ2H, δ13C, δ18O stable isotopic ratios, the spring waters and the majority of the gases are released through two consecutive fluid infiltration events. The preservation of the metamorphic signal of the upwelling H2O is linked to the local groundwater flow and fault abundancy. Furthermore, the noble gas isotopic ratios show a high degree of atmospheric contamination in the dissolved water gasses that is most likely related to the local hydrogeology. Nevertheless, the elevated corrected helium stable isotopic ratios (Rc/Ra) of our filtered data suggest that part of the emanating gases have a potential upper mantle source component. Beneath the Southeastern Carpathians, mantle fluids can have multiple origin including the dehydration of the sinking slab hosting the Vrancea seismogenic zone, the local asthenospheric upwelling and the lithospheric mantle itself. The flux of the mantle fluids is enhanced by lithospheric scale deformation zones that also support the fluid inflow from the upper mantle into the lower crust. The upwelling CO2–H2O mantle fluids may induce the release of crustal fluids by shifting the pore fluid composition (X(CO2)) and, consequently, initiating decarbonisation and devolatilization metamorphic reactions as a result of carbonate and hydrous mineral destabilisation in the crust. Based on the p-T-X(CO2) conditions of calc-silicates and the local low geotherm, we emphasise the importance of the upwelling fluids in the release and upward migration of further H2O and CO2 in the shallower lower and upper crust. Our observations in the Southeastern Carpathians show a strong similarity to other deep-seated deformation zones worldwide (e.g., Himalayas, Alps, San Andreas Fault). We infer that migration of deep fluids may also play an important role in addition to temperature control on the generation of crustal fluids in deep-seated deformation zones

Noble gas and carbon isotope systematics at the seemingly inactive Ciomadul volcano (Eastern‐Central Europe, Romania): evidence for volcanic degassing

Ciomadul is the youngest volcano in the Carpathian-Pannonian Region, Eastern-Central Europe, which last erupted 30 ka. This volcano is considered to be inactive, however, combined evidence from petrologic and magnetotelluric data, as well as seismic tomography studies suggest the existence of a subvolcanic crystal mush with variable melt content. The volcanic area is characterized by high CO2 gas output rate, with a minimum of 8.7 × 103 t yr-1. We investigated 31 gas emissions at Ciomadul to constrain the origin of the volatiles. The δ13C-CO2 and 3He/4He compositions suggest the outgassing of a significant component of mantle-derived fluids. The He isotope signature in the outgassing fluids (up to 3.10 Ra) is lower than the values in the peridotite xenoliths of the nearby alkaline basalt volcanic field (R/Ra 5.95Ra±0.01) which are representative of a continental lithospheric mantle and significantly lower than MORB values. Considering the chemical characteristics of the Ciomadul dacite, including trace element and Sr- Nd and O isotope compositions, an upper crustal contamination is less probable, whereas the primary magmas could have been derived from an enriched mantle source. The low He isotopic ratios could indicate a strongly metasomatized mantle lithosphere. This could be due to infiltration of subduction-related fluids and postmetasomatic ingrowth of radiogenic He. The metasomatic fluids are inferred to have contained subducted carbonate material resulting in a heavier carbon isotope composition (13C is in the range of -1.4 to -4.6 ‰) and an increase of CO2/3He ratio. Our study shows the magmatic contribution to the emitted gases

Selection of Conditions for Cellulase and Xylanase Extraction from Switchgrass Colonized by Acidothermus cellulolyticus

Solid-state fermentation has been widely used for enzyme production. However, secreted enzymes often bind to the solid substrate preventing their detection and recovery. A series of screening studies was performed to examine the role of extraction buffer composition including NaCl, ethylene glycol, sodium acetate buffer, and Tween 80, on xylanase and cellulase recovery from switchgrass. Our results indicated that the selection of an extraction buffer is highly dependent on the nature and source of the enzyme being extracted. While a buffer containing 50 mM sodium acetate at pH 5 was found to have a positive effect on the recovery of commercial fungal-derived cellulase and xylanase amended to switchgrass, the same buffer had a significant negative effect on enzyme extraction from solid fermentation samples colonized by the bacterium Acidothermus cellulolyticus. Xylanase activity was more affected by components in the extraction buffers compared to cellulase. This study demonstrated that extraction followed by diafiltration is important for assessing enzyme recovery from solid fermentation samples. Reduction in activity due to compounds present in the switchgrass extracts is reversible when the compounds are removed via diafiltration