Inhibitors of actin polymerization and calmodulin binding enhance protein kinase C-induced translocation of MARCKS in C6 glioma cells

AbstractMARCKS (myristoylated alanine-rich C-kinase substrate) is known to interact with calmodulin, actin filaments, and anionic phospholipids at a central basic domain which is also the site of phosphorylation by protein kinase C (PKC). In the present study, cytochalasin D (CD) and calmodulin antagonists were used to examine the influence of F-actin and calmodulin on membrane interaction of MARCKS in C6 glioma cells. CD treatment for 1 h disrupted F-actin filaments, increased membrane bound immunoreactive MARCKS (from 51% to 62% of total), yet markedly enhanced the amount of MARCKS translocated to the cytosolic fraction in response to the phorbol ester 4β-12-O-tetradecanoylphorbol 13-acetate. In contrast, CD treatment had no effect on phorbol ester-stimulated phosphorylation of MARCKS or on translocation of PKCα to the membrane fraction. Staurosporine also increased membrane association of MARCKS in a PKC-independent manner, as no change in MARCKS phosphorylation was noted and bis-indolylmaleimide (a more specific PKC inhibitor) did not alter MARCKS distribution. Staurosporine inhibited the phorbol ester-induced translocation of MARCKS but not of PKCα in both CD pretreated and untreated cells. Calmodulin antagonists (trifluoperazine, calmidazolium) had little effect on the cellular distribution or phosphorylation of MARCKS, but were synergistic with phorbol ester in translocating MARCKS from the membrane without a further increase in its phosphorylation. We conclude that cytoskeletal integrity is not required for phosphorylation and translocation of MARCKS in response to activated PKC, but that interaction with both F-actin and calmodulin might serve to independently modulate PKC-regulated localization and function of MARCKS at cellular membranes

The Very Low Albedo of WASP-12b From Spectral Eclipse Observations with Hubble\textit{Hubble}

We present an optical eclipse observation of the hot Jupiter WASP-12b using the Space Telescope Imaging Spectrograph on board the Hubble Space Telescope. These spectra allow us to place an upper limit of $A_g < 0.064$ (97.5% confidence level) on the planet's white light geometric albedo across 290--570 nm. Using six wavelength bins across the same wavelength range also produces stringent limits on the geometric albedo for all bins. However, our uncertainties in eclipse depth are $\sim$40% greater than the Poisson limit and may be limited by the intrinsic variability of the Sun-like host star --- the solar luminosity is known to vary at the $10^{-4}$ level on a timescale of minutes. We use our eclipse depth limits to test two previously suggested atmospheric models for this planet: Mie scattering from an aluminum-oxide haze or cloud-free Rayleigh scattering. Our stringent nondetection rules out both models and is consistent with thermal emission plus weak Rayleigh scattering from atomic hydrogen and helium. Our results are in stark contrast with those for the much cooler HD 189733b, the only other hot Jupiter with spectrally resolved reflected light observations; those data showed an increase in albedo with decreasing wavelength. The fact that the first two exoplanets with optical albedo spectra exhibit significant differences demonstrates the importance of spectrally resolved reflected light observations and highlights the great diversity among hot Jupiters.Comment: 8 pages, 4 figures, 1 table, published in ApJL, in pres

Gemini/GMOS Optical Transmission Spectroscopy of WASP-121b: signs of variability in an ultra-hot Jupiter?

We present ground-based, spectroscopic observations of two transits of the ultra-hot Jupiter WASP-121b covering the wavelength range $\approx$500 - 950 nm using Gemini/GMOS. We use a Gaussian process framework to model instrumental systematics in the light curves, and also demonstrate the use of the more generalised Student's-T process to verify our results. We find that our measured transmission spectrum, whilst showing overall agreement, is slightly discrepant with results obtained using HST/STIS, particularly for wavelengths shortward of $\approx$650 nm. In contrast to the STIS results, we find evidence for an increasing blueward slope and little evidence for absorption from either TiO or VO in our retrieval, in agreement with a number of recent studies performed at high-resolution. We suggest that this might point to some other absorbers, particularly some combination of recently detected atomic metals, in addition to scattering by hazes, being responsible for the excess optical absorption and observed vertical thermal inversion. Our results are also broadly consistent with previous ground-based photometry and 3D GCM predictions, however, these assumed different chemistry to our retrievals. In addition, we show that the GMOS observations are repeatable over short periods (days), similarly to the HST/STIS observations. Their difference over longer periods (months) could well be the result of temporal variability in the atmospheric properties (i.e. weather) as predicted by theoretical models of ultra-hot Jupiters; however, more mundane explanations such as instrumental systematics and stellar activity cannot be fully ruled out, and we encourage future observations to explore this possibility.Comment: 17 pages, 10 Figures. Accepted for publication in MNRA

Benefits for Type 2 Diabetes of Interrupting Prolonged Sitting With Brief Bouts of Light Walking or Simple Resistance Activities

OBJECTIVE To determine whether interrupting prolonged sitting with brief bouts of light-intensity walking (LW) or simple resistance activities (SRA) improves postprandial cardiometabolic risk markers in adults with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS In a randomized crossover trial, 24 inactive overweight/obese adults with T2D (14 men 62 ± 6 years old) underwent the following 8-h conditions on three separate days (with 6–14 days washout): uninterrupted sitting (control) (SIT), sitting plus 3-min bouts of LW (3.2 km · h−1) every 30 min, and sitting plus 3-min bouts of SRA (half-squats, calf raises, gluteal contractions, and knee raises) every 30 min. Standardized meals were consumed during each condition. Incremental areas under the curve (iAUCs) for glucose, insulin, C-peptide, and triglycerides were compared between conditions. RESULTS Compared with SIT, both activity-break conditions significantly attenuated iAUCs for glucose (SIT mean 24.2 mmol · h · L−1 [95% CI 20.4–28.0] vs. LW 14.8 [11.0–18.6] and SRA 14.7 [10.9–18.5]), insulin (SIT 3,293 pmol · h · L−1 [2,887–3,700] vs. LW 2,104 [1,696–2,511] and SRA 2,066 [1,660–2,473]), and C-peptide (SIT 15,641 pmol · h · L−1 [14,353–16,929] vs. LW 11,504 [10,209–12,799] and SRA 11,012 [9,723–12,301]) (all P < 0.001). The iAUC for triglycerides was significantly attenuated for SRA (P < 0.001) but not for LW (SIT 4.8 mmol · h · L−1 [3.6–6.0] vs. LW 4.0 [2.8–5.1] and SRA 2.9 [1.7–4.1]). CONCLUSIONS Interrupting prolonged sitting with brief bouts of LW or SRA attenuates acute postprandial glucose, insulin, C-peptide, and triglyceride responses in adults with T2D. With poor adherence to structured exercise, this approach is potentially beneficial and practical

Transiting Exoplanet Studies and Community Targets for JWST's Early Release Science Program

The James Webb Space Telescope will revolutionize transiting exoplanet atmospheric science due to its capability for continuous, long-duration observations and its larger collecting area, spectral coverage, and spectral resolution compared to existing space-based facilities. However, it is unclear precisely how well JWST will perform and which of its myriad instruments and observing modes will be best suited for transiting exoplanet studies. In this article, we describe a prefatory JWST Early Release Science (ERS) program that focuses on testing specific observing modes to quickly give the community the data and experience it needs to plan more efficient and successful future transiting exoplanet characterization programs. We propose a multi-pronged approach wherein one aspect of the program focuses on observing transits of a single target with all of the recommended observing modes to identify and understand potential systematics, compare transmission spectra at overlapping and neighboring wavelength regions, confirm throughputs, and determine overall performances. In our search for transiting exoplanets that are well suited to achieving these goals, we identify 12 objects (dubbed "community targets") that meet our defined criteria. Currently, the most favorable target is WASP-62b because of its large predicted signal size, relatively bright host star, and location in JWST's continuous viewing zone. Since most of the community targets do not have well-characterized atmospheres, we recommend initiating preparatory observing programs to determine the presence of obscuring clouds/hazes within their atmospheres. Measurable spectroscopic features are needed to establish the optimal resolution and wavelength regions for exoplanet characterization. Other initiatives from our proposed ERS program include testing the instrument brightness limits and performing phase-curve observations.(Abridged)Comment: This is a white paper that originated from an open discussion at the Enabling Transiting Exoplanet Science with JWST workshop held November 16 - 18, 2015 at STScI (http://www.stsci.edu/jwst/science/exoplanets). Accepted for publication in PAS

Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder

Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10-10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior

ACCESS & LRG-BEASTS: a precise new optical transmission spectrum of the ultrahot Jupiter WASP-103b

We present a new ground-based optical transmission spectrum of the ultrahot Jupiter WASP-103b ($T_{eq} = 2484$K). Our transmission spectrum is the result of combining five new transits from the ACCESS survey and two new transits from the LRG-BEASTS survey with a reanalysis of three archival Gemini/GMOS transits and one VLT/FORS2 transit. Our combined 11-transit transmission spectrum covers a wavelength range of 3900--9450A with a median uncertainty in the transit depth of 148 parts-per-million, which is less than one atmospheric scale height of the planet. In our retrieval analysis of WASP-103b's combined optical and infrared transmission spectrum, we find strong evidence for unocculted bright regions ($4.3\sigma$) and weak evidence for H$_2$O ($1.9\sigma$), HCN ($1.7\sigma$), and TiO ($2.1\sigma$), which could be responsible for WASP-103b's observed temperature inversion. Our optical transmission spectrum shows significant structure that is in excellent agreement with the extensively studied ultrahot Jupiter WASP-121b, for which the presence of VO has been inferred. For WASP-103b, we find that VO can only provide a reasonable fit to the data if its abundance is implausibly high and we do not account for stellar activity. Our results highlight the precision that can be achieved by ground-based observations and the impacts that stellar activity from F-type stars can have on the interpretation of exoplanet transmission spectra.Comment: 33 pages, 17 figures, 7 tables. Accepted for publication in A

Conifer DBMagic: a database housing multiple de novo transcriptome assemblies for 12 diverse conifer species

Conifers comprise an ancient and widespread plant lineage of enormous commercial and ecological value. However, compared to model woody angiosperms, such as Populus and Eucalyptus, our understanding of conifers remains quite limited at a genomic level. Large genome sizes (10,000–40,000 Mbp) and large amounts of repetitive DNA have limited efforts to produce a conifer reference genome, and genomic resource development has focused primarily on characterization of expressed sequences. Here, we report the completion of a conifer transcriptome sequencing project undertaken in collaboration with the U.S. DOE Joint Genome Institute that resulted in production of almost 12 million sequence reads. Five loblolly pine (Pinus taeda) cDNA libraries representing multiple tissues, treatments, and genotypes produced over four million sequence reads that, along with available Sanger expressed sequence tags, were used to create contig assemblies using three different assembly algorithms: Newbler, MiraEST, and NGen. In addition, libraries from 11 other conifer species, as well as one member of the Gnetales (Gnetum gnemon), produced 0.4 to 1.2 million sequence reads each. Among the selected conifer species were representatives of each of the seven phylogenetic families in the Coniferales: Araucariaceae, Cephalotaxaceae, Cupressaceae, Pinaceae, Podocarpaceae, Sciadopityaceae, and Taxaceae. Transcriptome builds for each species were generated using each of the three assemblers. All contigs for every species generated using each assembler can be obtained from Conifer DBMagic, a public database for searching, viewing, and downloading contig sequences, the associated sequence reads, and their annotations.Keywords: Database, Gene models, Pinus, Comparative phylogenomics, Annotation, Transcriptome, Coniferale