The Effect of Cancer Cachexia Progression on the Feeding Regulation of Skeletal Muscle Protein Turnover

Cancer cachexia is defined as the unintentional loss of skeletal muscle mass with or without fat loss that cannot be reversed by conventional nutritional support. Cachexia occurs in ~20% of cancer patients. More specifically, 50% of lung cancer patients, the most common cancer worldwide, develop cachexia. Cachexia occurs most often in lung and gastrointestinal cancers, whereas breast and prostate have the lowest rate of cachexia. Cancer-induced cachexia disrupts skeletal muscle protein turnover (decreasing protein synthesis and increasing protein degradation). Skeletal muscle’s capacity for protein synthesis is highly sensitive to local and systemic stimuli that are controlled by mTORC1 and AMPK signaling. During cachexia, altered protein turnover is thought to occur through suppressed anabolic signaling via mTORC1, coinciding with the chronic activation of AMPK. While progress has been made in understanding some of the mechanisms underlying the suppressed anabolic signaling in cachectic muscle, gaps still remain in our understanding of muscle’s ability to respond to anabolic stimulus prior to cachexia development. The purpose of this study was to determine if cachexia progression disrupts the feeding regulation of AMPK signaling and if gp130 signaling and muscle contraction could regulate this process. Specific aim 1 examined the feeding regulation of skeletal muscle protein synthesis in pre-cachectic tumor bearing mice. Feeding increased muscle protein synthesis, while lowering AMPK signaling in pre-cachectic tumor bearing mice. Importantly, pre-cachectic tumor bearing mice have overall suppressed muscle protein synthesis independent of the fast or fed condition. Muscle specific AMPK loss was sufficient to improve the fasting suppression of muscle mTORC1 and protein synthesis in pre-cachectic tumor bearing mice. Specific aim 2 examined if muscle gp130 signaling regulates the feeding regulation of AMPK during cancer cachexia progression. Muscle gp130 loss lowered the fasting induction of AMPK in pre-cachectic tumor bearing mice without improving protein synthesis. Muscle gp130 loss did not alter the feeding regulation of muscle Akt/mTORC1 signaling and protein synthesis. Specific Aim 3 examined if an acute bout of muscle contractions could improve the muscle protein synthesis response to feeding during the progression of cachexia. Pre-cachectic tumor bearing mice exhibit suppressed protein synthesis in response low frequency electrical stimulation, and the inability to synergistically induce protein synthesis in response to feeding and contraction. In summary, pre-cachectic tumor bearing mice have lowered Akt/mTORC1 signaling and protein synthesis. Feeding can induce Akt/mTORC1 and protein synthesis and AMPK regulates the fasting suppression of protein synthesis in pre-cachectic tumor bearing mice. While gp130 loss reduces AMPK it is not sufficient to improve protein synthesis in pre-cachectic tumor bearing mice. The added protein synthesis response to feeding and contraction is blunted in pre-cachectic tumor bearing mice. These findings provide novel insight into the regulation of Akt/mTORC1 signaling and protein synthesis in response to feeding. Additionally, these studies highlight gp130’s regulation of AMPK prior to cachexia development, and the blunted anabolic muscle response to feeding and contraction in pre-cachectic tumor bearing mice. By understanding these intracellular signaling processes and perturbations prior to cachexia development, we will be able to elucidate potential therapeutic targets and treatment options to manipulate and prevent cancer cachexia

A Nonparametric Variance-Ratio Test of the Behavior of U.K. Real Estate and Construction Indices

This study utilizes tests based on ranks and signs suggested by Wright (2000), in addition to the traditional variance-ratio test, to examine the behavior of United Kingdom real estate and construction security indices. The results suggest a positive dependence in the index return series and provide a strong rejection of the random walk hypothesis for the two U.K. index series examined in this study. Thus, the efficient market hypothesis (EMH) is not confirmed for these real estate securities indices in the U.K.variance ratio; heteroskedasticity; stock index; random walk; ranks; signsJournal: International Real Estate Review

Photometric type Ia supernova surveys in narrow band filters

We study the characteristics of a narrow band type Ia supernova survey through simulations based on the upcoming Javalambre Physics of the accelerating universe Astrophysical Survey (J-PAS). This unique survey has the capabilities of obtaining distances, redshifts, and the SN type from a single experiment thereby circumventing the challenges faced by the resource-intensive spectroscopic follow-up observations. We analyse the flux measurements signal-to-noise ratio and bias, the supernova typing performance, the ability to recover light curve parameters given by the SALT2 model, the photometric redshift precision from type Ia supernova light curves and the effects of systematic errors on the data. We show that such a survey is not only feasible but may yield large type Ia supernova samples (up to 250 supernovae at $z<0.5$ per month of search) with low core collapse contamination ($\sim 1.5$ per cent), good precision on the SALT2 parameters (average $\sigma_{m_B}=0.063$, $\sigma_{x_1}=0.47$ and $\sigma_c=0.040$) and on the distance modulus (average $\sigma_{\mu}=0.16$, assuming an intrinsic scatter $\sigma_{\mathrm{int}}=0.14$), with identified systematic uncertainties $\sigma_{\mathrm{sys}}\lesssim 0.10 \sigma_{\mathrm{stat}}$. Moreover, the filters are narrow enough to detect most spectral features and obtain excellent photometric redshift precision of $\sigma_z=0.005$, apart from $\sim$ 2 per cent of outliers. We also present a few strategies for optimising the survey's outcome. Together with the detailed host galaxy information, narrow band surveys can be very valuable for the study of supernova rates, spectral feature relations, intrinsic colour variations and correlations between supernova and host galaxy properties, all of which are important information for supernova cosmological applications.Comment: 20 pages, 12 tables and 26 figures. Version accepted by MNRAS, with results slightly different from previous on

The ACS survey of globular clusters. XIII. Photometric calibration in comparison with Stetson standards

In this study we compare the photometric data of 34 Milky Way globular clusters, observed within the ACS Treasury Program (PI: Ata Sarajedini) with the corresponding ground-based data, provided by the Photometric Standard Field Catalogs of Stetson (2000, 2005). We focus on the transformation between the HST/ACS F606W to V-band and F814W to I-band only. The goal is to assess the validity of the filter transformation equations by Sirianni et al.(2005) with respect to their dependence on metallicity, Horizontal Branch morphology, mass and integrated (V-I) colour of the various globular clusters. Such a dependence is expected due to the fact that the transformation equations are based on the observations of only one globular cluster, i.e., NGC 2419. Surprisingly, the correlation between offset and metallicity is found to be weak, with a low level significance. The correlation between offset and Horizontal Branch structure, as well as total cluster mass is still weaker. Based on the available data we do not find the photometric offset to be linked to multiple stellar populations, e.g., as found in NGC 0288, NGC 1851, and NGC 5139. The results of this study show that there are small systematic offsets between the transformed ACS- and observed ground based photometry, and that these are only weakly correlated, if at all, with various cluster parameters and their underlying stellar populations. As a result, investigators wishing to transform globular cluster photometry from the Sirianni et al.(2005) ground-based V, I system onto the Stetson (2000) system simply need to add 0.040 (+/-0.012) to the V-band magnitudes and 0.047 (+/-0.011) to the I-band magnitudes. This in turn means that the transformed ACS (V-I) colours match the ground-based values from Stetson (2000) to within ~0.01 mag.Comment: 28 pages, 14 figures, accepted for publication in ApJ

The ACS Survey of Galactic Globular Clusters: M54 and Young Populations in the Sagittarius Dwarf Spheroidal Galaxy

We present new Hubble Space Telescope photometry of the massive globular cluster M54 (NGC 6715) and the superposed core of the tidally disrupted Sagittarius (Sgr) dSph galaxy as part of the ACS Survey of Galactic Globular Clusters. Our deep (F606W~26.5), high-precision photometry yields an unprecedentedly detailed color-magnitude diagram showing the extended blue horizontal branch and multiple main sequences of the M54+Sgr system. The distance and reddening to M54 are revised usingboth isochrone and main-sequence fitting to (m-M)_0=17.27 and E(B-V)=0.15. Preliminary assessment finds the M54+Sgr field to be dominated by the old metal-poor populations of Sgr and the globular cluster. Multiple turnoffs indicate the presence of at least two intermediate-aged star formation epochs with 4 and 6 Gyr ages and [Fe/H]=-0.4 to -0.6. We also clearly show, for the first time, a prominent, 2.3 Gyr old Sgr population of near-solar abundance. A trace population of even younger (0.1-0.8 Gyr old), more metal-rich ([Fe/H]\sim0.6) stars is also indicated. The Sgr age-metallicity relation is consistent with a closed-box model and multiple (4-5) star formation bursts over the entire life of the satellite, including the time since Sgr began disrupting.Comment: Accepted to ApJ Letter; 11 pages, 2 figures; figure 1 uploaded as jpg; paper in ApJ format with full-resolution figures available at: http://www.astro.ufl.edu/~ata/public_hstgc/paperIV/paperIV.p

The ACS Survey of Galactic Globular Clusters. III. The Double Subgiant Branch of NGC 1851

Photometry with HST's ACS reveals that the subgiant branch (SGB) of the globular cluster NGC 1851 splits into two well-defined branches. If the split is due only to an age effect, the two SGBs would imply two star formation episodes separated by $\sim$ 1 Gyr. We discuss other anomalies in NGC 1851 which could be interpreted in terms of a double stellar population. Finally, we compare the case of NGC 1851 with the other two globulars known to host multiple stellar populations, and show that all three clusters differ in several important respects.Comment: 22 pages, 7 figures, accepted for pubblication on Ap

The GALANTE Photometric System

This paper describes the characterization of the GALANTE photometric system, a seven intermediate- and narrow-band filter system with a wavelength coverage from 3000 $\r{A}$ to 9000 $\r{A}$ . We describe the photometric system presenting the full sensitivity curve as a product of the filter sensitivity, CCD, telescope mirror, and atmospheric transmission curves, as well as some first- and second-order moments of this sensitivity function. The GALANTE photometric system is composed of four filters from the J-PLUS photometric system, a twelve broad-to-narrow filter system, and three exclusive filters, specifically designed to measure the physical parameters of stars such as effective temperature $T_{\rm eff}$, $\log(g)$, metallicity, colour excess $E(4405-5495)$, and extinction type $R_{5495}$. Two libraries, the Next Generation Spectral Library (NGSL) and the one presented in Ma\'iz Apell\'aniz & Weiler (2018), have been used to determine the transformation equations between the Sloan Digital Sky Survey ($\textit{SDSS}$) $\textit{ugriz}$ photometry and the GALANTE photometric system. We will use this transformation to calibrate the zero points of GALANTE images. To this end, a preliminary photometric calibration of GALANTE has been made based on two different $\textit{griz}$ libraries ($\textit{SDSS}$ DR12 and ATLAS All-Sky Stellar Reference Catalog, hereinafter $\textit{RefCat2}$). A comparison between both zero points is performed leading us to the choice of $\textit{RefCat2}$ as the base catalogue for this calibration, and applied to a field in the Cyg OB2 association.Comment: Accepted in MNRA

Competitive inhibition of natural antisense Sok-RNA interactions activates Hok-mediated cell killing in Escherichia coli

Short regulatory RNAs are widespread in bacteria, and many function through antisense recognition of mRNA. Among the best studied antisense transcripts are RNA antitoxins that repress toxin mRNA translation. The hok/sok locus of plasmid R1 from Escherichia coli is an established model for RNA antitoxin action. Base-pairing between hok mRNA and Sok-antisense-RNA increases plasmid maintenance through post-segregational-killing of plasmid-free progeny cells. To test the model and the idea that sequestration of Sok-RNA activity could provide a novel antimicrobial strategy, we designed anti Sok peptide nucleic acid (PNA) oligomers that, according to the model, would act as competitive inhibitors of hok mRNA::Sok-RNA interactions. In hok/sok-carrying cells, anti Sok PNAs were more bactericidal than rifampicin. Also, anti Sok PNAs induced ghost cell morphology and an accumulation of mature hok mRNA, consistent with cell killing through synthesis of Hok protein. The results support the sense/antisense model for hok mRNA repression by Sok-RNA and demonstrate that antisense agents can be used to out-compete RNA::RNA interactions in bacteria. Finally, BLAST analyses of ≈200 prokaryotic genomes revealed that many enteric bacteria have multiple hok/sok homologous and analogous RNA-regulated toxin–antitoxin loci. Therefore, it is possible to activate suicide in bacteria by targeting antitoxins

Evaluation of the MODIS Albedo Product over a Heterogeneous Agricultural Area

In this article, the Moderate Resolution Imaging Spectroradiometer (MODIS) Bidirectional Reflectance Distribution Function (BRDF)/Albedo product (MCD43) is evaluated over a heterogeneous agricultural area in the framework of the Earth Observation: Optical Data Calibration and Information Extraction (EODIX) project campaign, which was developed in Barrax (Spain) in June 2011. In this method, two models, the RossThick-LiSparse-Reciprocal (RTLSR) (which corresponds to the MODIS BRDF algorithm) and the RossThick-Maignan-LiSparse-Reciprocal (RTLSR-HS), were tested over airborne data by processing high-resolution images acquired with the Airborne Hyperspectral Scanner (AHS) sensor. During the campaign, airborne images were retrieved with different view zenith angles along the principal and orthogonal planes. Comparing the results of applying the models to the airborne data with ground measurements, we obtained a root mean square error (RMSE) of 0.018 with both RTLSR and RTLSR-HS models. The evaluation of the MODIS BRDF/Albedo product (MCD43) was performed by comparing satellite images with AHS estimations. The results reported an RMSE of 0.04 with both models. Additionally, taking advantage of a homogeneous barley pixel, we compared in situ albedo data to satellite albedo data. In this case, the MODIS albedo estimation was (0.210 +/- 0.003), while the in situ measurement was (0.204 +/- 0.003). This result shows good agreement in regard to a homogeneous pixel