Water delivery by pebble accretion to rocky planets in habitable zones in evolving disks

The Earth's ocean mass is only 2.3 x 10^{-4} of the whole planet mass. Even including water in the interior, it would be at most 10^{-3}-10^{-2}. Ancient Mars may have had a similar or slightly smaller water fraction. It is important to clarify the water delivery mechanism to rocky planets in habitable zones in exoplanetary systems, as well as that to the Earth and Mars. Here, we consider water delivery to planets by icy pebbles after the snowline inwardly passes the planetary orbits and derive the water mass fraction (f_{water}) of the final planet as a function of disk parameters and discuss the parameters that reproduce f_{water} comparable to that inferred for the Earth and ancient Mars. We calculate the growth of icy pebbles and their radial drift with a 1D model, and accretion of icy pebbles onto planets, by simultaneously solving the snowline migration and the disk dissipation, to evaluate f_{water} of the planets. We find that f_{water} is regulated by the total mass (M_{res}) of icy dust materials preserved in the outer disk regions at the timing (t = t_{snow}) of the snowline passage of the planetary orbit. Because M_{res} decays rapidly after the pebble formation front reaches the disk outer edge (at t = t_{pff}), f_{water} is sensitive to the ratio t_{snow}/t_{pff}, which is determined by the disk parameters. We find t_{snow}/t_{pff} 10 is important. Deriving an analytical formula for f_{water} that reproduces the numerical results, we find that f_{water} of a rocky planet near 1 au is ~ 10^{-4}-10^{-2}, in the disks with initial disk size ~ 30-50 au and the initial disk mass accretion rate ~ (10^{-8}-10^{-7}) M_sun/y. Because these disks may be median or slightly compact/massive disks, the water fraction of rocky planets in habitable zones may be often similar to that of the Earth, if the icy pebble accretion is responsible for the water delivery.Comment: published in A&A; this is a corrected version from the published versio

AKARI Mission Program: Excavating Mass Loss History in Extended Dust Shells of Evolved Stars (MLHES) I. Far-IR Photometry

We performed a far-IR imaging survey of the circumstellar dust shells of 144 evolved stars as a mission programme of the AKARI infrared astronomical satellite using the Far-Infrared Surveyor (FIS) instrument. With this survey, we deliver far-IR surface brightness distributions of roughly 10' x 40' or 10' x 20' areas of the sky around the target evolved stars in the four FIS bands at 65, 90, 140, and 160 microns. Our objectives are to characterize the far-IR surface brightness distributions of the cold dust component in the circumstellar dust shells, from which we derive the amount of cold dust grains as low as 20 K and empirically establish the history of the early mass loss history. In this first installment of the series, we introduce the project and its aims, describe the observations, data reduction, and surface brightness correction process, and present the entire data set along with the results of integrated photometry measurements (i.e., the central source and circumstellar dust shell altogether). We find that (1) far-IR emission is detected from all but one object at the spatial resolution about 30" - 50" in the corresponding bands, (2) roughly 60 - 70 % of the target sources show some extension, (3) previously unresolved nearby objects in the far-IR are now resolved around 28 target sources, (4) the results of photometry measurements are reasonable with respect to the entries in the AKARI/FIS Bright Source Catalogue, despite the fact that the targets are assumed to be point-sources when catalogue flux densities were computed, and (5) an IR two-color diagram would place the target sources in a roughly linear distribution that may correlate with the age of the circumstellar dust shell and can potentially be used to identify which targets are more extended than others.Comment: To be published in PASJ AKARI Special Issue: 25 pages, 5 figures, 5 tables (and 28 supplementary figures available only in PASJ on-line

Nilotinib exerts antiparkinsonian actions

Abnormal motor behaviors in Parkinson’s disease (PD) result from striatal dysfunction due to an imbalance between dopamine and glutamate transmissions that are integrated by dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32). c-Abelson tyrosine kinase (c-Abl) phosphorylates cyclin-dependent kinase 5 (Cdk5) at Tyr15 to increase the activity of Cdk5, which reduces the efficacy of dopaminergic signaling by phosphorylating DARPP-32 at Thr75 in the striatum. Here, we report that in the mouse striatum, a novel c-Abl inhibitor, nilotinib (AMN107), inhibits phosphorylation of both Cdk5 at Tyr15 and DARPP-32 at Thr75, which is negatively regulated by dopamine receptor activation through a D2 receptor-mediated mechanism. Like a D2-agonist, nilotinib synergizes with a D1-agonist for inducing striatal c-Fos expression. Moreover, systemic administration of nilotinib normalizes striatal motor behaviors in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. These findings suggest that nilotinib could possibly serve as a new and alternative agent for treating PD motor symptoms

Predicting dust extinction properties of star-forming galaxies from H-alpha/UV ratio

Using star-forming galaxies sample in the nearby Universe (0.02<z<0.10) selected from the SDSS (DR7) and GALEX all-sky survey (GR5), we present a new empirical calibration for predicting dust extinction of galaxies from H-alpha-to-FUV flux ratio. We find that the H-alpha dust extinction (A(Ha)) derived with H-alpha/H-beta ratio (Balmer decrement) increases with increasing H-alpha/UV ratio as expected, but there remains a considerable scatter around the relation, which is largely dependent on stellar mass and/or H-alpha equivalent width (EW(Ha)). At fixed H-alpha/UV ratio, galaxies with higher stellar mass (or galaxies with lower EW(Ha)) tend to be more highly obscured by dust. We quantify this trend and establish an empirical calibration for predicting A(Ha) with a combination of H-alpha/UV ratio, stellar mass and EW(Ha), with which we can successfully reduce the systematic uncertainties accompanying the simple H-alpha/UV approach by ~15-30%. The new recipes proposed in this study will provide a convenient tool for predicting dust extinction level of galaxies particularly when Balmer decrement is not available. By comparing A(Ha) (derived with Balmer decrement) and A(UV) (derived with IR/UV luminosity ratio) for a subsample of galaxies for which AKARI FIR photometry is available, we demonstrate that more massive galaxies tend to have higher extra extinction towards the nebular regions compared to the stellar continuum light. Considering recent studies reporting smaller extra extinction towards nebular regions for high-redshift galaxies, we argue that the dust geometry within high-redshift galaxies resemble more like low-mass galaxies in the nearby Universe.Comment: 14 pages, 14 figures, Accepted for publication in MNRA

c-Abl Inhibition Exerts Antiparkinsonian Effects

Parkinson’s disease (PD) is caused by a progressive degeneration of nigral dopaminergic cells leading to striatal dopamine deficiency. From the perspective of antiparkinsonian drug mechanisms, pharmacologic treatment of PD can be divided into symptomatic and disease-modifying (neuroprotective) therapies. An increase in the level and activity of the Abelson non-receptor tyrosine kinase (c-Abl) has been identified in both human and mouse brains under PD conditions. In the last decade, it has been observed that the inhibition of c-Abl activity holds promise for protection against the degeneration of nigral dopaminergic cells in PD and thereby exerts antiparkinsonian effects. Accordingly, c-Abl inhibitors have been applied clinically as a disease-modifying therapeutic strategy for PD treatment. Moreover, in a series of studies, including that presented here, experimental evidence suggests that in a mouse model of parkinsonism induced by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, c-Abl inhibition exerts an immediate effect improving motor impairments by normalizing altered activity in striatal postsynaptic signaling pathways mediated by Cdk5 (cyclin-dependent kinase 5) and DARPP-32 (dopamine- and cyclic AMP-regulated phosphoprotein 32 kDa). Based on this, we suggest that c-Abl inhibitors represent an ideal antiparkinsonian agent that has both disease-modifying and symptomatic effects. Future research is required to carefully evaluate the therapeutic efficacy and clinical challenges associated with applying c-Abl inhibitors to the treatment of PD

Defect of Adaptation to Hypoxia in Patients With COPD Due to Reduction of Histone Deacetylase 7

BackgroundHypoxia inducible factor (HIF)-1 plays an important role in cellular adaptation to hypoxia by activating oxygen-regulated genes such as vascular endothelial growth factor (VEGF) and erythropoietin. Sputum VEGF levels are reported to be decreased in COPD, despite hypoxia. Here we show that patients with COPD fail to induce HIF-1α and VEGF under hypoxic condition because of a reduction in histone deacetylase (HDAC) 7.MethodsPeripheral blood mononuclear cells (PBMCs) were obtained from patients with moderate to severe COPD (n = 21), smokers without COPD (n = 12), and nonsmokers (n = 15). PBMCs were exposed to hypoxia (1% oxygen, 5% CO2, and 94% N2) for 24 h, and HIF-1α and HDAC7 protein expression in nuclear extracts were determined by sodium dodecyl sulfate poly acrylamide gel electrophoresis (SDS-PAGE)/Western blotting.ResultsHIF-1α was significantly induced by hypoxia in each group when compared with the normoxic condition (12-fold induction in nonsmokers, 24-fold induction in smokers without COPD, fourfold induction in COPD), but induction of HIF-1α under hypoxia was significantly lower in patients with COPD than in nonsmokers and smokers without COPD (P < .05 and P < .01, respectively). VEGF messenger RNA detected by quantitative real-time polymerase chain reaction was correlated with HIF-1α protein in nuclei (r = 0.79, P < .05), and HDAC7 protein expression was correlated with HIF-1α protein in nuclei (r = 0.46, P < .05). HDAC7 knockdown inhibited hypoxia-induced HIF-1α activity in U937 cells, and HIF-1α nuclear translocation and HIF-1α binding to the VEGF promoter in A549 cells.ConclusionsHDAC7 reduction in COPD causes a defect of HIF-1α induction response to hypoxia with impaired VEGF gene expression. This poor cellular adaptation might play a role in the pathogenesis of COPD

Histone deacetylase 2–mediated deacetylation of the glucocorticoid receptor enables NF-κB suppression

Glucocorticoids are the most effective antiinflammatory agents for the treatment of chronic inflammatory diseases even though some diseases, such as chronic obstructive pulmonary disease (COPD), are relatively glucocorticoid insensitive. However, the molecular mechanism of this glucocorticoid insensitivity remains uncertain. We show that a defect of glucocorticoid receptor (GR) deacetylation caused by impaired histone deacetylase (HDAC) 2 induces glucocorticoid insensitivity toward nuclear factor (NF)-κB–mediated gene expression. Specific knockdown of HDAC2 by RNA interference resulted in reduced sensitivity to dexamethasone suppression of interleukin 1β–induced granulocyte/macrophage colony-stimulating factor production. Loss of HDAC2 did not reduce GR nuclear translocation, GR binding to glucocorticoid response element (GRE) on DNA, or GR-induced DNA or gene induction but inhibited the association between GR and NF-κB. GR becomes acetylated after ligand binding, and HDAC2-mediated GR deacetylation enables GR binding to the NF-κB complex. Site-directed mutagenesis of K494 and K495 reduced GR acetylation, and the ability to repress NF-κB–dependent gene expression becomes insensitive to histone deacetylase inhibition. In conclusion, we show that overexpression of HDAC2 in glucocorticoid-insensitive alveolar macrophages from patients with COPD is able to restore glucocorticoid sensitivity. Thus, reduction of HDAC2 plays a critical role in glucocorticoid insensitivity in repressing NF-κB–mediated, but not GRE-mediated, gene expression

Striatal Cdk5-pTyr15

Striatal functions depend on the activity balance between the dopamine and glutamate neurotransmissions. Glutamate inputs activate cyclin-dependent kinase 5 (Cdk5), which inhibits postsynaptic dopamine signaling by phosphorylating DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) at Thr75 in the striatum. c-Abelson tyrosine kinase (c-Abl) is known to phosphorylate Cdk5 at Tyr15 (Tyr15-Cdk5) and thereby facilitates the Cdk5 activity. We here report that Cdk5 with Tyr15 phosphorylation (Cdk5-pTyr15) is enriched in the mouse striatum, where dopaminergic stimulation inhibited phosphorylation of Tyr15-Cdk5 by acting through the D2 class dopamine receptors. Moreover, in the 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP) mouse model, dopamine deficiency caused increased phosphorylation of both Tyr15-Cdk5 and Thr75-DARPP-32 in the striatum, which could be attenuated by administration of L-3,4-dihydroxyphenylalanine and imatinib (STI-571), a selective c-Abl inhibitor. Our results suggest a functional link of Cdk5-pTyr15 with postsynaptic dopamine and glutamate signals through the c-Abl kinase activity in the striatum