Rapid, buoyancy-driven ice-sheet retreat of hundreds of metres per day.

Rates of ice-sheet grounding-line retreat can be quantified from the spacing of corrugation ridges on deglaciated regions of the seafloor1,2, providing a long-term context for the approximately 50-year satellite record of ice-sheet change3-5. However, the few existing examples of these landforms are restricted to small areas of the seafloor, limiting our understanding of future rates of grounding-line retreat and, hence, sea-level rise. Here we use bathymetric data to map more than 7,600 corrugation ridges across 30,000 km2 of the mid-Norwegian shelf. The spacing of the ridges shows that pulses of rapid grounding-line retreat, at rates ranging from 55 to 610 m day-1, occurred across low-gradient (±1°) ice-sheet beds during the last deglaciation. These values far exceed all previously reported rates of grounding-line retreat across the satellite3,4,6,7 and marine-geological1,2 records. The highest retreat rates were measured across the flattest areas of the former bed, suggesting that near-instantaneous ice-sheet ungrounding and retreat can occur where the grounding line approaches full buoyancy. Hydrostatic principles show that pulses of similarly rapid grounding-line retreat could occur across low-gradient Antarctic ice-sheet beds even under present-day climatic forcing. Ultimately, our results highlight the often-overlooked vulnerability of flat-bedded areas of ice sheets to pulses of extremely rapid, buoyancy-driven retreat.

Inter-decadal climate variability induces differential ice response along Pacific-facing West Antarctica.

West Antarctica has experienced dramatic ice losses contributing to global sea-level rise in recent decades, particularly from Pine Island and Thwaites glaciers. Although these ice losses manifest an ongoing Marine Ice Sheet Instability, projections of their future rate are confounded by limited observations along West Antarctica's coastal perimeter with respect to how the pace of retreat can be modulated by variations in climate forcing. Here, we derive a comprehensive, 12-year record of glacier retreat around West Antarctica's Pacific-facing margin and compare this dataset to contemporaneous estimates of ice flow, mass loss, the state of the Southern Ocean and the atmosphere. Between 2003 and 2015, rates of glacier retreat and acceleration were extensive along the Bellingshausen Sea coastline, but slowed along the Amundsen Sea. We attribute this to an interdecadal suppression of westerly winds in the Amundsen Sea, which reduced warm water inflow to the Amundsen Sea Embayment. Our results provide direct observations that the pace, magnitude and extent of ice destabilization around West Antarctica vary by location, with the Amundsen Sea response most sensitive to interdecadal atmosphere-ocean variability. Thus, model projections accounting for regionally resolved ice-ocean-atmosphere interactions will be important for predicting accurately the short-term evolution of the Antarctic Ice Sheet.

Antarctic Seabed Assemblages in an Ice-Shelf-Adjacent Polynya, Western Weddell Sea.

Ice shelves cover ~1.6 million km2 of the Antarctic continental shelf and are sensitive indicators of climate change. With ice-shelf retreat, aphotic marine environments transform into new open-water spaces of photo-induced primary production and associated organic matter export to the benthos. Predicting how Antarctic seafloor assemblages may develop following ice-shelf loss requires knowledge of assemblages bordering the ice-shelf margins, which are relatively undocumented. This study investigated seafloor assemblages, by taxa and functional groups, in a coastal polynya adjacent to the Larsen C Ice Shelf front, western Weddell Sea. The study area is rarely accessed, at the frontline of climate change, and located within a CCAMLR-proposed international marine protected area. Four sites, ~1 to 16 km from the ice-shelf front, were explored for megabenthic assemblages, and potential environmental drivers of assemblage structures were assessed. Faunal density increased with distance from the ice shelf, with epifaunal deposit-feeders a surrogate for overall density trends. Faunal richness did not exhibit a significant pattern with distance from the ice shelf and was most variable at sites closest to the ice-shelf front. Faunal assemblages significantly differed in composition among sites, and those nearest to the ice shelf were the most dissimilar; however, ice-shelf proximity did not emerge as a significant driver of assemblage structure. Overall, the study found a biologically-diverse and complex seafloor environment close to an ice-shelf front and provides ecological baselines for monitoring benthic ecosystem responses to environmental change, supporting marine management.

Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory.

Maternal protein malnutrition throughout pregnancy and lactation compromises brain development in late gestation and after birth, affecting structural, biochemical, and pathway dynamics with lasting consequences for motor and cognitive function. However, the importance of nutrition during the preimplantation period for brain development is unknown. We have previously shown that maternal low-protein diet (LPD) confined to the preimplantation period (Emb-LPD) in mice, with normal nutrition thereafter, is sufficient to induce cardiometabolic and locomotory behavioral abnormalities in adult offspring. Here, using a range of in vivo and in vitro techniques, we report that Emb-LPD and sustained LPD reduce neural stem cell (NSC) and progenitor cell numbers at E12.5, E14.5, and E17.5 through suppressed proliferation rates in both ganglionic eminences and cortex of the fetal brain. Moreover, Emb-LPD causes remaining NSCs to up-regulate the neuronal differentiation rate beyond control levels, whereas in LPD, apoptosis increases to possibly temper neuron formation. Furthermore, Emb-LPD adult offspring maintain the increase in neuron proportion in the cortex, display increased cortex thickness, and exhibit short-term memory deficit analyzed by the novel-object recognition assay. Last, we identify altered expression of fragile X family genes as a potential molecular mechanism for adverse programming of brain development. Collectively, these data demonstrate that poor maternal nutrition from conception is sufficient to cause abnormal brain development and adult memory loss.

A model of the recruitment-derecruitment and volume of lung units in an excised lung as it is inflated-deflated between minimum and maximum lung volume.

The role of the recruitment-derecruitment of small structures in the lung (lung units) as the lung increases and decreases in volume has been debated. The objective of this study was to develop a model to estimate the change in the number and volume of open lung units as an excised lung is inflated-deflated between minimum and maximum lung volume. The model was formulated based on the observation that the compliance of the slowly changing quasi-static pressure-volume (P-V) curve of an excised rat lung can differ from the compliance of a faster changing small sinusoidal pressure volume perturbations superimposed on the curve. In those regions of the curve where differences in compliance occur, the lung tissue properties exhibit nonlinear characteristics, which cannot be linearized using "incremental" or "small signal" analysis. The model attributes the differences between the perturbation and quasi-static compliance to an additional nonlinear compliance term that results from the sequential opening and closing of lung units. Using this approach, it was possible to calculate the normalized average volume and the normalized number of open units as the lung is slowly inflated-deflated. Results indicate that the normalized average volume and the normalized number of open units are not linearly related to normalized lung volume, and at equal lung volumes the normalized number of open units is greater and the normalized average lung unit volume is smaller during lung deflation when compared to lung inflation. In summary, a model was developed to describe the recruitment-derecruitment process in excised lungs based on the differences between small signal perturbation compliance and quasi-static compliance. Values of normalized lung unit volume and the normalized number of open lung units were shown to be nonlinear functions of both transpulmonary pressure and normalized lung volume.

Pulmonary and cardiovascular responses of rats to inhalation of a commercial antimicrobial spray containing titanium dioxide nanoparticles.

Our laboratory has previously demonstrated that application of an antimicrobial spray product containing titanium dioxide (TiO(2)) generates an aerosol of titanium dioxide in the breathing zone of the applicator. The present report describes the design of an automated spray system and the characterization of the aerosol delivered to a whole body inhalation chamber. This system produced stable airborne levels of TiO(2) particles with a median count size diameter of 110 nm. Rats were exposed to 314 mg/m(3) min (low dose), 826 mg/m(3) min (medium dose), and 3638 mg/m(3) min (high dose) of TiO(2) under the following conditions: 2.62 mg/m(3) for 2 h, 1.72 mg/m(3) 4 h/day for 2 days, and 3.79 mg/m(3) 4 h/day for 4 days, respectively. Pulmonary (breathing rate, specific airway resistance, inflammation, and lung damage) and cardiovascular (the responsiveness of the tail artery to constrictor or dilatory agents) endpoints were monitored 24 h post-exposure. No significant pulmonary or cardiovascular changes were noted at low and middle dose levels. However, the high dose caused significant increases in breathing rate, pulmonary inflammation, and lung cell injury. Results suggest that occasional consumer use of this antimicrobial spray product should not be a hazard. However, extended exposure of workers routinely applying this product to surfaces should be avoided. During application, care should be taken to minimize exposure by working under well ventilated conditions and by employing respiratory protection as needed. It would be prudent to avoid exposure to children or those with pre-existing respiratory disease.

Mutational screening of VSX1 in keratoconus patients from the European population.

PURPOSE: To perform mutational screening of the visual system homeobox gene 1 (VSX1; MIM#605020) in patients with sporadic and familial keratoconus (MIM#148300) in a European population and, for the first time, report the mutational analysis of the two newly identified VSX1exons. METHODS: VSX1sequence variants in patients with keratoconus were evaluated by direct sequencing of the entire coding region, including two novel exons. In familial keratoconus cases, segregation of potentially pathogenic VSX1variants was assessed to determine pathogenicity. Transcript analysis was carried out on splice site and synonymous sequence variants not detected in controls. RESULTS: A total of 66 unrelated patients with keratoconus from the European population (27 with familial keratoconus; 39 with sporadic keratoconus) were analysed for VSX1 mutations. Four sequence variants were not observed in 100 healthy control individuals: c.432C>G (p.D144E), c.479G>A (p.G160D), c.789C>T (p.S263S), and an intronic change c.844-13T>A (numbered with respect to NM_014588). Segregation was not detected for p.D144E and c.844-13T>A. The change in p.G160D was observed in two patients with sporadic keratoconus. Although predicted to alter VSX1 splicing, p.S263S had no effect on transcript processing. Four known SNPs were detected and the following polymorphic variants were observed in keratoconus patients and controls: c.711T>A (NM_199425; p.P237P), c.844-5_-6insT (NM_014588), c.*28G>T (DQ854811/DQ854812), and c.*50G>A (DQ854809/DQ854810). CONCLUSIONS: VSX1has a minor role in keratoconus pathogenesis. The pathogenicity of p.G160D remains controversial and this change may represent a rare polymorphism or genetic modifier. Further evidence is provided that the previously reported variant, p.D144E, is a polymorphism.

A system for recording high fidelity cough sound and airflow characteristics.

Cough is considered an early sign of many respiratory diseases. Recently, there has been increased interest in measuring, analyzing, and characterizing the acoustical properties of a cough. In most cases the main focus of those studies was to distinguish between involuntary coughs and ambient sounds over a specified time period. The objective of this study was to develop a system to measure high fidelity voluntary cough sounds to detect lung diseases. To further augment the analysis capability of the system, a non-invasive flow measurement was also incorporated into the design. One of the main design considerations was to increase the fidelity of the recorded sound characteristics by increasing the signal to noise ratio of cough sounds and to minimize acoustical reflections from the environment. To accomplish this goal, a system was designed with a mouthpiece connected to a cylindrical tube. A microphone was attached near the mouthpiece so that its diaphragm was tangent to the inner surface of the cylinder. A pneumotach at the end of the tube measured the airflow generated by the cough. The system was terminated with an exponential horn to minimize sound reflections. Custom software was developed to read, process, display, record, and analyze cough sound and airflow characteristics. The system was optimized by comparing acoustical reflections and total signal to background noise ratios across different designs. Cough measurements were also collected from volunteer subjects to assess the viability of the system. Results indicate that analysis of cough characteristics has the potential to detect lung disease.

Nanoparticle inhalation impairs coronary microvascular reactivity via a local reactive oxygen species-dependent mechanism.

We have shown that nanoparticle inhalation impairs endothelium-dependent vasodilation in coronary arterioles. It is unknown whether local reactive oxygen species (ROS) contribute to this effect. Rats were exposed to TiO(2) nanoparticles via inhalation to produce a pulmonary deposition of 10 microg. Coronary arterioles were isolated from the left anterior descending artery distribution, and responses to acetylcholine, arachidonic acid, and U46619 were assessed. Contributions of nitric oxide synthase and prostaglandin were assessed via competitive inhibition with N(G)-Monomethyl-L-Arginine (L-NMMA) and indomethacin. Microvascular wall ROS were quantified via dihydroethidium (DHE) fluorescence. Coronary arterioles from rats exposed to nano-TiO(2) exhibited an attenuated vasodilator response to ACh, and this coincided with a 45% increase in DHE fluorescence. Coincubation with 2,2,6,6-tetramethylpiperidine-N-oxyl and catalase ameliorated impairments in ACh-induced vasodilation from nanoparticle exposed rats. Incubation with either L-NMMA or indomethacin significantly attenuated ACh-induced vasodilation in sham-control rats, but had no effect in rats exposed to nano-TiO(2). Arachidonic acid induced vasoconstriction in coronary arterioles from rats exposed to nano-TiO(2), but dilated arterioles from sham-control rats. These results suggest that nanoparticle exposure significantly impairs endothelium-dependent vasoreactivity in coronary arterioles, and this may be due in large part to increases in microvascular ROS. Furthermore, altered prostanoid formation may also contribute to this dysfunction. Such disturbances in coronary microvascular function may contribute to the cardiac events associated with exposure to particles in this size range.

Observation of a large atomic parity violation effect in ytterbium.

Atomic parity violation has been observed in the 6s(2 1)S(0)-->5d6s(3)D(1) 408-nm forbidden transition of ytterbium. The parity-violating amplitude is found to be 2 orders of magnitude larger than in cesium, where the most precise experiments to date have been performed. This is in accordance with theoretical predictions and constitutes the largest atomic parity-violating amplitude yet observed. This also opens the way to future measurements of neutron distributions and anapole moments by comparing parity-violating amplitudes for various isotopes and hyperfine components of the transition.

Nanoparticle inhalation impairs endothelium-dependent vasodilation in subepicardial arterioles.

Exposure to fine particulate matter (PM, mean aerodynamic diameter

Ultracold bosons in a tilted multilevel double-well potential.

The N-body problem in a tilted double well requires new features for macroscopic quantum superposition in ultracold atoms. In particular, one needs to go beyond the single-particle ground state in each well. We provide explicit criteria for when two energy levels are needed to describe the state space. For typical experimental parameters, two levels are indeed required for the creation of macroscopic superposition states. Furthermore, we show that a small tilt causes the collapse of such states. However, partial macroscopic superposition states reappear when the tilt can be compensated by atom-atom interactions.

Increased susceptibility of the lungs of hyperthyroid rats to oxidant injury: specificity of effects.

Results from previous studies indicate that hyperthyroidism increases the risk of ozone-induced lung toxicity. This observation raised the possibility that pulmonary damage from other oxidant substances might be greater in a hyperthyroid state. To address this hypothesis, pulmonary responses to crystalline silica, a particulate with oxidant properties, were evaluated in normal or hyperthyroid adult male rats. To induce a hyperthyroid condition, time-release pellets containing thyroxine were implanted subcutaneously; control rats received placebo pellets. After 7 days, the animals were exposed to saline or silica (0.1mg/100g BW or 1.0mg/100g BW) by intratracheal instillation. Following silica treatment, there was a dose-related increase in bronchoalveolar lavage (BAL) albumin levels and neutrophil numbers. However, the effects of silica were similar in both normal and hyperthyroid rats. These findings were confirmed and contrasted with those regarding ozone (1ppm, 4h inhalation) in a subsequent experiment. The results indicated that, although exposure to either ozone or silica resulted in increases in BAL albumin levels and neutrophil numbers, only responses to ozone were enhanced in hyperthyroid rats. These findings suggest that specificity exists in regards to the modulation of oxidant-induced lung damage and inflammation by thyroid hormones.

Increased susceptibility of hyperthyroid rats to ozone: early events and mechanisms.

Previous studies demonstrated that ozone-induced lung damage and inflammation are much greater in hyperthyroid rats, compared to normal rats, at 18 h postexposure. The purpose of the present investigation was to study early events and mechanisms underlying the increased sensitivity to ozone in a hyperthyroid state. Specifically, the degree of lung epithelial cell barrier disruption, the antioxidant status of the extracellular lining fluid, and the release of inflammatory mediators were examined. To induce a hyperthyroid state, mature male Sprague-Dawley rats were implanted with time-release pellets containing thyroxine; control rats received placebo pellets. After 7 d, the animals were exposed to air or ozone (2 ppm, 3 h). Immediately following the end of the exposure, bronchoalveolar lavage (BAL) fluid and cells were harvested. BAL fluid albumin levels and total antioxidant status were examined. In addition, levels of prostaglandin E2 (PGE2), macrophage inflammatory protein (MIP)-2, MCP-1, and tumor necrosis factor (TNF)-alpha were determined in BAL fluid and in media samples following ex vivo culture of BAL cells harvested after in vivo inhalation exposures. The results of this study are consistent with the following hypotheses: (1) A marked increase in the permeability of the alveolar-capillary barrier is an early event following ozone exposure in a hyperthyroid state; however this does not appear to be due to overall changes in BAL fluid antioxidant potential. (2) Early increases in MIP-2, but not PGE2, are involved in the enhanced lung response to ozone in a hyperthyroid state. (3) Inflammatory mediator production (i.e., PGE2, MIP-2, MCP-1, and TNF-alpha) by alveolar macrophages plays a minimal role in the initial responses to ozone in a hyperthyroid state.

Delayed hepcidin response explains the lag period in iron absorption following a stimulus to increase erythropoiesis.

INTRODUCTION: The delay of several days between an erythropoietic stimulus and the subsequent increase in intestinal iron absorption is commonly believed to represent the time required for body signals to programme the immature crypt enterocytes and for these cells to migrate to the villus. Recent data however suggest that signals from the body to alter absorption are mediated by circulating hepcidin and that this peptide exerts its effect on mature villus enterocytes. METHODS: We have examined the delay in the absorptive response following stimulated erythropoiesis using phenylhydrazine induced haemolysis and correlated this with expression of hepcidin in the liver and iron transporters in the duodenum. RESULTS: There was a delay of four days following haemolysis before a significant increase in iron absorption was observed. Hepatic hepcidin expression did not decrease until day 3, reaching almost undetectable levels by days 4 and 5. This coincided with the increase in duodenal expression of divalent metal transporter 1, duodenal cytochrome b, and Ireg1. CONCLUSION: These results suggest that the delayed increase in iron absorption following stimulated erythropoiesis is attributable to a lag in the hepcidin response rather than crypt programming, and are consistent with a direct effect of the hepcidin pathway on mature villus enterocytes.

Keratoconus: an analysis of corneal asymmetry.

BACKGROUND: Keratoconus, a non-inflammatory corneal ectasia, is reported to have bilateral involvement in over 90% of patients. The purpose of this study was to quantify the extent of asymmetry of disease at presentation to a regional corneal clinic. METHODS: Eighty three patients diagnosed at presentation, using a combination of videokeratography, slit lamp examination, and refractive findings were retrospectively selected. On this basis, 73 patients were designated as having evidence of keratoconus in both eyes. In order to quantify the degree of asymmetry between fellow eyes in these bilateral patients, intraclass correlation was calculated for best spectacle corrected visual acuity (BSCVA) and for 13 different topographical indices generated using videokeratography. In order to examine the link between each index and visual function, the intrapatient differences in each index were compared to the intrapatient differences in BSCVA using Pearson's correlation. RESULTS: BSCVA showed a high degree of asymmetry between fellow eyes with a correlation coefficient of r = 0.006. With the exception of area analysed, all of the topographical indices also showed disparity between paired eyes (r = 0.01 to r = 0.25). Pearson's analysis found that the intrapatient differences in the standard deviation of the power (SDP), average corneal power (ACP), central corneal power (K), as well as the composite keratoconus prediction index (KPI) inversely correlated with the intrapatient differences in best spectacle corrected acuity (r = -0.76,-0.75,-0.69, and -0.73 respectively). CONCLUSIONS: This study demonstrates, quantitatively, the asymmetry of disease found in patients at the point of initial diagnosis of keratoconus. It also suggests that increases in indices which reflect various aspects of corneal power as well as the composite index KPI correlate with a decrease in BSCVA.

Changes in the expression of intestinal iron transport and hepatic regulatory molecules explain the enhanced iron absorption associated with pregnancy in the rat.

BACKGROUND: Iron absorption increases during pregnancy to cater for the increased iron requirements of the growing fetus. AIMS: To investigate the role of the duodenal iron transport molecules and hepatic regulatory molecules in coordinating the changes in iron absorption observed during pregnancy. METHODS: Rats at various days of gestation and 24-48 hours post-partum were examined for hepatic expression of hepcidin, transferrin receptors 1 and 2, and HFE (the gene mutated in the most prevalent form of hereditary haemochromatosis), and duodenal expression of divalent metal transporter 1 (DMT1), duodenal cytochrome b (Dcytb), iron regulated mRNA (Ireg1), and hephaestin (Hp) by ribonuclease protection assay, western blotting, and immunohistochemistry. RESULTS: Decreased hepatic non-haem iron and transferrin saturation and increased expression of transferrin receptor 1 in the liver indicated a progressive reduction in maternal body iron stores during pregnancy. Duodenal expression of the iron transport molecules DMT1, Dcytb, and Ireg1 increased during pregnancy, and this corresponded with a reduction in hepcidin, HFE, and transferrin receptor 2 expression in the liver. Expression of all molecules returned towards control values by 24-48 hours post-partum. CONCLUSIONS: These data indicate that increased expression of key iron transport molecules is responsible for the elevated iron absorption associated with pregnancy, and implicate hepcidin, HFE, and transferrin receptor 2 in determining how the maternal iron homeostatic machinery responds to the increased iron demands accompanying gestation.

Effects of paving asphalt fume exposure on genotoxic and mutagenic activities in the rat lung.

Asphalt fumes are complex mixtures of aerosols and vapors containing various organic compounds, including polycyclic aromatic hydrocarbons (PAHs). Previously, we have demonstrated that inhalation exposure of rats to asphalt fumes resulted in dose-dependent induction of CYP1A1 with concomitant down-regulation of CYP2B1 and increased phase II enzyme quinone reductase activity in the rat lung. In the present study, the potential genotoxic effects of asphalt fume exposure due to altered lung microsomal enzymes were studied. Rats were exposed to air or asphalt fume generated under road paving conditions at various concentrations and sacrificed the next day. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage and examined for DNA damage using the comet assay. To evaluate the systemic genotoxic effect of asphalt fume, micronuclei formation in bone marrow polychromatic erythrocytes (PCEs) was monitored. Lung S9 from various exposure groups was isolated from tissue homogenates and characterized for metabolic activity in activating 2-aminoanthracene (2-AA) and benzo[a]pyrene (BaP) mutagenicity using the Ames test with Salmonella typhimurium YG1024 and YG1029. This study showed that the paving asphalt fumes significantly induced DNA damage in AM, as revealed by DNA migration in the comet assay, in a dose-dependent manner, whereas the micronuclei formation in bone marrow PCEs was not detected even at a very high exposure level (1733 mg h/m3). The conversion of 2-AA to mutagens in the Ames test required lung S9-mediated metabolic activation in a dose-dependent manner. In comparison to the controls, lung S9 from rats exposed to asphalt fume at a total exposure level of 479+/-33 mg h/m3 did not significantly enhance 2-AA mutagenicity with either S. typhimurium YG1024 or YG1029. At a higher total asphalt fume exposure level (1150+/-63 mg h/m3), S9 significantly increased the mutagenicity of 2-AA as compared to the control. However, S9 from asphalt fume-exposed rats did not significantly activate the mutagenicity of BaP in the Ames test. These results show that asphalt fume exposure, which significantly altered both phases I and II metabolic enzymes in lung microsomes, is genotoxic to AM and enhances the metabolic activation of certain mutagens through altered S9 content.