Evolution of gene expression changes in newborn rats after mechanical ventilation with reversible intubation

Mechanical ventilation (MV) is life-saving but potentially harmful for lungs of premature infants. So far, animal models dealt with the acute impact of MV on immature lungs, but less with its delayed effects. We used a newborn rodent model including non-surgical and therefore reversible intubation with moderate ventilation and hypothesized that there might be distinct gene expression patterns after a ventilation-free recovery period compared to acute effects directly after MV. Newborn rat pups were subjected to 8 hr of MV with 60% oxygen (O(2)), 24 hr after injection of lipopolysaccharide (LPS), intended to create a low inflammatory background as often recognized in preterm infants. Animals were separated in controls (CTRL), LPS injection (LPS), or full intervention with LPS and MV with 60% O(2) (LPS + MV + O(2)). Lungs were recovered either directly following (T:0 hr) or 48 hr after MV (T:48 hr). Histologically, signs of ventilator-induced lung injury (VILI) were observed in LPS + MV + O(2) lungs at T:0 hr, while changes appeared similar to those known from patients with chronic lung disease (CLD) with fewer albeit larger gas exchange units, at T:48 hr. At T:0 hr, LPS + MV + O(2) increased gene expression of pro-inflammatory MIP-2. In parallel anti-inflammatory IL-1Ra gene expression was increased in LPS and LPS + MV + O(2) groups. At T:48 hr, pro- and anti-inflammatory genes had returned to their basal expression. MMP-2 gene expression was decreased in LPS and LPS + MV + O(2) groups at T:0 hr, but no longer at T:48 hr. MMP-9 gene expression levels were unchanged directly after MV. However, at T:48 hr, gene and protein expression increased in LPS + MV + O(2) group. In conclusion, this study demonstrates the feasibility of delayed outcome measurements after a ventilation-free period in newborn rats and may help to further understand the time-course of molecular changes following MV. The differences obtained from the two time points could be interpreted as an initial transitory increase of inflammation and a delayed impact of the intervention on structure-related genes.

Experimental dissolution of molybdenum-sulphides at low oxygen concentrations: A first-order approximation of late Archean atmospheric conditions

The abundance of atmospheric oxygen and its evolution through Earth's history is a highly debated topic. The earliest change of the Mo concentration and isotope composition of marine sediments are interpreted to be linked to the onset of the accumulation of free O2 in Earth's atmosphere. The O2 concentration needed to dissolve significant amounts of Mo in water is not yet quantified, however. We present laboratory experiments on pulverized and surface-cleaned molybdenite (MoS2) and a hydrothermal breccia enriched in Mo-bearing sulphides using a glove box setup. Duration of an experiment was 14 days, and first signs of oxidation and subsequent dissolution of Mo compounds start to occur above an atmospheric oxygen concentration of 72 ± 20 ppmv (i.e., 2.6 to 4.6 × 10−4 present atmospheric level (PAL)). This experimentally determined value coincides with published model calculations supporting atmospheric O2 concentrations between 1 × 10−5 to 3 × 10−4 PAL prior to the Great Oxidation Event and sets an upper limit to the molecular oxygen needed to trigger Mo accumulation and Mo isotope variations recorded in sediments. In combination with the published Mo isotope composition of the rock record, this result implies an atmospheric oxygen concentration prior to 2.76 Ga of below 72 ± 20 ppmv.

Dating prograde fluid pulses during subduction by in situ U–Pb and oxygen isotope analysis

Keywords High-pressure fluids · Whiteschists · U–Pb dating · Oxygen isotopes · Ion microprobe · Metasomatism Introduction The subduction of crustal material to mantle depths and its chemical modification during burial and exhumation contribute to element recycling in the mantle and the formation of new crust through arc magmatism. Crustal rocks that Abstract The Dora-Maira whiteschists derive from metasomatically altered granites that experienced ultrahighpressure metamorphism at ~750 °C and 40 kbar during the Alpine orogeny. In order to investigate the P–T–time– fluid evolution of the whiteschists, we obtained U–Pb ages from zircon and monazite and combined those with trace element composition and oxygen isotopes of the accessory minerals and coexisting garnet. Zircon cores are the only remnants of the granitic protolith and still preserve a Permian age, magmatic trace element compositions and δ18O of ~10 ‰. Thermodynamic modelling of Si-rich and Si-poor whiteschist compositions shows that there are two main fluid pulses during prograde subduction between 20 and 40 kbar. In Si-poor samples, the breakdown of chlorite to garnet + fluid occurs at ~22 kbar. A first zircon rim directly overgrowing the cores has inclusions of prograde phlogopite and HREE-enriched patterns indicating zircon growth at the onset of garnet formation. A second main fluid pulse is documented close to peak metamorphic conditions in both Si-rich and Si-poor whiteschist when talc + kyanite react to garnet + coesite + fluid. A second metamorphic overgrowth on zircon with HREE depletion was observed in the Si-poor whiteschists, whereas a single metamorphic overgrowth capturing phengite and talc inclusions was observed in the Si-rich whiteschists. Garnet rims, zircon rims and monazite are in chemical and isotopic equilibrium for oxygen, demonstrating that they all formed at peak metamorphism at 35 Ma as constrained by the age of monazite (34.7 ± 0.4 Ma) and zircon rims (35.1 ± 0.8 Ma). The prograde zircon rim in Si-poor whiteschists has an age that is within error indistinguishable from the age of peak metamorphic conditions, consistent with a minimum rate of subduction of 2 cm/year for the Dora-Maira unit. Oxygen isotope values for zircon rims, monazite and garnet are equal within error at 6.4 ± 0.4 ‰, which is in line with closed-system equilibrium fractionation during prograde to peak temperatures. The resulting equilibrium Δ18Ozircon-monazite at 700 ± 20 °C is 0.1 ± 0.7 ‰. The in situ oxygen isotope data argue against an externally derived input of fluids into the whiteschists. Instead, fluidassisted zircon and monazite recrystallisation can be linked to internal dehydration reactions during prograde subduction. We propose that the major metasomatic event affecting the granite protolith was related to hydrothermal seafloor alteration post-dating Jurassic rifting, well before the onset of Alpine subduction.