The impact of SPARC on age-related cardiac dysfunction and fibrosis in Drosophila

Tissue fibrosis, an accumulation of extracellular matrix proteins such as collagen, accompanies cardiac ageing in humans and this is linked to an increased risk of cardiac failure. The mechanisms driving age-related tissue fibrosis and cardiac dysfunction are unclear, yet clinically important. Drosophila is amenable to the study of cardiac ageing as well as collagen deposition; however it is unclear whether collagen accumulates in the ageing Drosophila heart. This work examined collagen deposition and cardiac function in ageing Drosophila, in the context of reduced expression of collagen-interacting protein SPARC (Secreted Protein Acidic and Rich in Cysteine) an evolutionarily conserved protein linked with fibrosis. Heart function was measured using high frame rate videomicroscopy. Collagen deposition was monitored using a fluorescently-tagged collagen IV reporter (encoded by the Viking gene) and staining of the cardiac collagen, Pericardin. The Drosophila heart accumulated collagen IV and Pericardin as flies aged. Associated with this was a decline in cardiac function. SPARC heterozygous flies lived longer than controls and showed little to no age-related cardiac dysfunction. As flies of both genotypes aged, cardiac levels of collagen IV (Viking) and Pericardin increased similarly. Over-expression of SPARC caused cardiomyopathy and increased Pericardin deposition. The findings demonstrate that, like humans, the Drosophila heart develops a fibrosis-like phenotype as it ages. Although having no gross impact on collagen accumulation, reduced SPARC expression extended Drosophila lifespan and cardiac health span. It is proposed that cardiac fibrosis in humans may develop due to the activation of conserved mechanisms and that SPARC may mediate cardiac ageing by mechanisms more subtle than gross accumulation of collagen

Characterization of a set of abdominal neuroendocrine cells that regulate stress physiology using colocalized diuretic peptides in Drosophila

Multiple neuropeptides are known to regulate water and ion balance in Drosophila melanogaster. Several of these peptides also have other functions in physiology and behavior. Examples are corticotropin-releasing factor-like diuretic hormone (diuretic hormone 44; DH44) and leucokinin (LK), both of which induce fluid secretion by Malpighian tubules (MTs), but also regulate stress responses, feeding, circadian activity and other behaviors. Here, we investigated the functional relations between the LK and DH44 signaling systems. DH44 and LK peptides are only colocalized in a set of abdominal neurosecretory cells (ABLKs). Targeted knockdown of each of these peptides in ABLKs leads to increased resistance to desiccation, starvation and ionic stress. Food ingestion is diminished by knockdown of DH44, but not LK, and water retention is increased by LK knockdown only. Thus, the two colocalized peptides display similar systemic actions, but differ with respect to regulation of feeding and body water retention. We also demonstrated that DH44 and LK have additive effects on fluid secretion by MTs. It is likely that the colocalized peptides are coreleased from ABLKs into the circulation and act on the tubules where they target different cell types and signaling systems to regulate diuresis and stress tolerance. Additional targets seem to be specific for each of the two peptides and subserve regulation of feeding and water retention. Our data suggest that the ABLKs and hormonal actions are sufficient for many of the known DH44 and LK functions, and that the remaining neurons in the CNS play other functional roles

Formation of toxaphene-like contaminants during simulated paper pulp bleaching

Toxaphene is a persistent pesticide which is highly toxic to a broad range of organisms including freshwater fish. The sources of Toxaphene are still not clearly understood. Atmospheric transport from the cotton growing districts of the southeastern United States is presently considered the most plausible hypothesis. This mechanism, however, does not adequately explain all of the data on Toxaphene concentrations in different geographical regions of the U.S. In particular, concentrations in the immediate vicinity of the Great Lakes have been increasing, whereas decreases have been observed at Midwestern sites not near these lakes. It is conceivable that environmental chlorination reactions, not involving the manufacture or application of Toxaphene at all, may be generating materials closely related to or indistinguishable from Toxaphene. The objective of our research was to simulate pulp bleaching conditions in the laboratory and determine if Toxaphene-like materials could be produced. The aqueous chlorination of the monoterpenes, camphene, limonene, apinene and 8-pinene produced complex polychlorinated product mixtures. The extent of chlorination was primarily dependent on pH and light conditions. At pH 2 and exposed to sunlight product mixtures were obtained that had striking similarities to Toxaphene. At higher pH or in the dark, less extensive but still substantial chlorination took place; these lower chlorinated compounds could be mistaken for biologically degraded Toxaphene in environmental samples. We conclude that Toxaphene-like mixtures may conceivably be formed under environmental conditions, but the actual extent of formation of such mixtures and the degree to which they may contribute to apparent Toxaphene in natural samples remain to be assessed.U.S. Department of the InteriorU.S. Geological SurveyOpe

The atmospheric circulation of the super Earth GJ 1214b: Dependence on composition and metallicity

We present three-dimensional atmospheric circulation models of GJ 1214b, a 2.7 Earth-radius, 6.5 Earth-mass super Earth detected by the MEarth survey. Here we explore the planet's circulation as a function of atmospheric metallicity and atmospheric composition, modeling atmospheres with a low mean-molecular weight (i.e., H2-dominated) and a high mean-molecular weight (i.e. water- and CO2-dominated). We find that atmospheres with a low mean-molecular weight have strong day-night temperature variations at pressures above the infrared photosphere that lead to equatorial superrotation. For these atmospheres, the enhancement of atmospheric opacities with increasing metallicity lead to shallower atmospheric heating, larger day-night temperature variations and hence stronger superrotation. In comparison, atmospheres with a high mean-molecular weight have larger day-night and equator-to-pole temperature variations than low mean-molecular weight atmospheres, but differences in opacity structure and energy budget lead to differences in jet structure. The circulation of a water-dominated atmosphere is dominated by equatorial superrotation, while the circulation of a CO2-dominated atmosphere is instead dominated by high-latitude jets. By comparing emergent flux spectra and lightcurves for 50x solar and water-dominated compositions, we show that observations in emission can break the degeneracy in determining the atmospheric composition of GJ 1214b. The variation in opacity with wavelength for the water-dominated atmosphere leads to large phase variations within water bands and small phase variations outside of water bands. The 50x solar atmosphere, however, yields small variations within water bands and large phase variations at other characteristic wavelengths. These observations would be much less sensitive to clouds, condensates, and hazes than transit observations.Comment: 12 pages, 11 figures, 2 tables, accepted to Ap

Retrieval of atmospheric properties of cloudy L dwarfs

© 2017 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.We present the first results from applying the spectral inversion technique in the cloudy L dwarf regime. Our new framework provides a flexible approach to modelling cloud opacity which can be built incrementally as the data requires, and improves upon previous retrieval experiments in the brown dwarf regime by allowing for scattering in two stream radiative transfer. Our first application of the tool to two mid-L dwarfs is able to reproduce their near-infrared spectra far more closely than grid models. Our retrieved thermal, chemical, and cloud profiles allow us to estimate $T_{\rm eff} = 1796^{+23}_{-25}$ K and $\log g = 5.21^{+0.05}_{-0.08}$ for 2MASS J05002100+0330501 and for 2MASSW J2224438-015852 we find $T_{\rm eff} = 1723^{+18}_{-19}$ K and $\log g = 5.31^{+0.04}_{-0.08}$, in close agreement with previous empirical estimates. Our best model for both objects includes an optically thick cloud deck which passes $\tau_{cloud} \geq 1$ (looking down) at a pressure of around 5 bar. The temperature at this pressure is too high for silicate species to condense, and we argue that corundum and/or iron clouds are responsible for this cloud opacity. Our retrieved profiles are cooler at depth, and warmer at altitude than the forward grid models that we compare, and we argue that some form of heating mechanism may be at work in the upper atmospheres of these L dwarfs. We also identify anomalously high CO abundance in both targets, which does not correlate with the warmth of our upper atmospheres or our choice of cloud model, and find similarly anomalous alkali abundance for one of our targets. These anomalies may reflect unrecognised shortcomings in our retrieval model, or inaccuracies in our gas phase opacities.Peer reviewedFinal Accepted Versio

Masses, Radii, and Cloud Properties of the HR 8799 Planets

The near-infrared colors of the planets directly imaged around the A star HR 8799 are much redder than most field brown dwarfs of the same effective temperature. Previous theoretical studies of these objects have concluded that the atmospheres of planets b, c, and d are unusually cloudy or have unusual cloud properties. Some studies have also found that the inferred radii of some or all of the planets disagree with expectations of standard giant planet evolution models. Here we compare the available data to the predictions of our own set of atmospheric and evolution models that have been extensively tested against observations of field L and T dwarfs, including the reddest L dwarfs. Unlike some previous studies we require mutually consistent choices for effective temperature, gravity, cloud properties, and planetary radius. This procedure thus yields plausible values for the masses, effective temperatures, and cloud properties of all three planets. We find that the cloud properties of the HR 8799 planets are not unusual but rather follow previously recognized trends, including a gravity dependence on the temperature of the L to T spectral transition--some reasons for which we discuss. We find the inferred mass of planet b is highly sensitive to whether or not we include the H and K band spectrum in our analysis. Solutions for planets c and d are consistent with the generally accepted constraints on the age of the primary star and orbital dynamics. We also confirm that, like in L and T dwarfs and solar system giant planets, non-equilibrium chemistry driven by atmospheric mixing is also important for these objects. Given the preponderance of data suggesting that the L to T spectral type transition is gravity dependent, we present an exploratory evolution calculation that accounts for this effect. Finally we recompute the the bolometric luminosity of all three planets.Comment: 52 pages, 12 figures, Astrophysical Journal, in press. v2 features minor editorial updates and correction

Coordinated RNA-Seq and peptidomics identify neuropeptides and G-protein coupled receptors (GPCRs) in the large pine weevil Hylobius abietis, a major forestry pest

Hylobius abietis (Linnaeus), or large pine weevil (Coleoptera, Curculionidae), is a pest of European coniferous forests. In order to gain understanding of the functional physiology of this species, we have assembled a de novo transcriptome of H. abietis, from sequence data obtained by Next Generation Sequencing. In particular, we have identified genes encoding neuropeptides, peptide hormones and their putative G-protein coupled receptors (GPCRs) to gain insights into neuropeptide-modulated processes. The transcriptome was assembled de novo from pooled paired-end, sequence reads obtained from RNA from whole adults, gut and central nervous system tissue samples. Data analysis was performed on the transcripts obtained from the assembly including, annotation, gene ontology and functional assignment as well as transcriptome completeness assessment and KEGG pathway analysis. Pipelines were created using Bioinformatics tools and techniques for prediction and identification of neuropeptides and neuropeptide receptors. Peptidomic analysis was also carried out using a combination of MALDI-TOF as well as Q-Exactive Orbitrap mass spectrometry to confirm the identified neuropeptide. 41 putative neuropeptide families were identified in H. abietis, including Adipokinetic hormone (AKH), CAPA and DH31. Neuropeptide F, which has not been yet identified in the model beetle T. castaneum, was identified. Additionally, 24 putative neuropeptide and 9 leucine-rich repeat containing G protein coupled receptor-encoding transcripts were determined using both alignment as well as non-alignment methods. This information, submitted to the NCBI sequence read archive repository (SRA accession: SRP133355), can now be used to inform understanding of neuropeptide-modulated physiology and behaviour in H. abietis; and to develop specific neuropeptide-based tools for H. abietis control

Twitchy, the Drosophila orthologue of the ciliary gating protein FBF1/dyf-19, is required for coordinated locomotion and male fertility

Primary cilia are compartmentalised from the rest of the cell by a ciliary gate comprising transition fibres and a transition zone. The ciliary gate allows the selective import and export of molecules such as transmembrane receptors and transport proteins. These are required for the assembly of the cilium, its function as a sensory and signalling centre and to maintain its distinctive composition. Certain motile cilia can also form within the cytosol as exemplified by human and Drosophila sperm. The role of transition fibre proteins has not been well described in the cytoplasmic cilia. Drosophila have both compartmentalised primary cilia, in sensory neurons, and sperm flagella that form within the cytosol. Here, we describe phenotypes for twitchy the Drosophila orthologue of a transition fibre protein, mammalian FBF1/C. elegans dyf-19. Loss-of-function mutants in twitchy are adult lethal and display a severely uncoordinated phenotype. Twitchy flies are too uncoordinated to mate but RNAi-mediated loss of twitchy specifically within the male germline results in coordinated but infertile adults. Examination of sperm from twitchy RNAi-knockdown flies shows that the flagellar axoneme forms, elongates and is post-translationally modified by polyglycylation but the production of motile sperm is impaired. These results indicate that twitchy is required for the function of both sensory cilia that are compartmentalised from the rest of the cell and sperm flagella that are formed within the cytosol of the cell. Twitchy is therefore likely to function as part of a molecular gate in sensory neurons but may have a distinct function in sperm cells.ISSN:2046-639