The Extragalactic Distance Database: Color-Magnitude Diagrams

The CMDs/TRGB (Color-Magnitude Diagrams/Tip of the Red Giant Branch) section of the Extragalactic Distance Database contains a compilation of observations of nearby galaxies from the Hubble Space Telescope. Approximately 250 (and increasing) galaxies in the Local Volume have CMDs and the stellar photometry tables used to produce them available through the web. Various stellar populations that make up a galaxy are visible in the CMDs, but our primary purpose for collecting and analyzing these galaxy images is to measure the TRGB in each. We can estimate the distance to a galaxy by using stars at the TRGB as standard candles. In this paper we describe the process of constructing the CMDs and make the results available to the public.Comment: 8 pages, 5 figures, 1 long table, submitted to Astronomical Journa

A New Distance to The Antennae Galaxies (NGC 4038/39) Based on the Type Ia Supernova 2007sr

Traditionally, the distance to NGC 4038/39 has been derived from the systemic recession velocity, yielding about 20 Mpc for H_0 = 72 km/s/Mpc. Recently, this widely adopted distance has been challenged based on photometry of the presumed tip of the red giant branch (TRGB), which seems to yield a shorter distance of 13.3+-1.0 Mpc and, with it, nearly 1 mag lower luminosities and smaller radii for objects in this prototypical merger. Here we present a new distance estimate based on observations of the Type Ia supernova (SN) 2007sr in the southern tail, made at Las Campanas Observatory as part of the Carnegie Supernova Project. The resulting distance of D(SN Ia) = 22.3+-2.8 Mpc [(m-M)_0 = 31.74+-0.27 mag] is in good agreement with a refined distance estimate based on the recession velocity and the large-scale flow model developed by Tonry and collaborators, D(flow) = 22.5+-2.8 Mpc. We point out three serious problems that a short distance of 13.3 Mpc would entail, and trace the claimed short distance to a likely misidentification of the TRGB. Reanalyzing Hubble Space Telescope (HST) data in the Archive with an improved method, we find a TRGB fainter by 0.9 mag and derive from it a preliminary new TRGB distance of D(TRGB) = 20.0+-1.6 Mpc. Finally, assessing our three distance estimates we recommend using a conservative, rounded value of D = 22+-3 Mpc as the best currently available distance to The Antennae.Comment: 8 pages, 5 figures, 1 table (emulateapj; uses amsmath package). Accepted for publication in The Astronomical Journal, Vol. 136. Figs. 1 & 2 degraded to reduce file size

Loss of m(1)acp(3)Ψ ribosomal RNA modification is a major feature of cancer

The ribosome is an RNA-protein complex that is essential for translation in all domains of life. The structural and catalytic core of the ribosome is its ribosomal RNA (rRNA). While mutations in ribosomal protein (RP) genes are known drivers of oncogenesis, oncogenic rRNA variants have remained elusive. We identify a cancer-specific single-nucleotide variation in 18S rRNA at nucleotide 1248.U in up to 45.9% of patients with colorectal carcinoma (CRC) and present across >22 cancer types. This is the site of a unique hyper-modified base, 1-methyl-3-α-amino-α-carboxyl-propyl pseudouridine (m(1)acp(3)Ψ), a >1-billion-years-conserved RNA modification at the peptidyl decoding site of the ribosome. A subset of CRC tumors we call hypo-m(1)acp(3)Ψ shows sub-stoichiometric m(1)acp(3)Ψ modification, unlike normal control tissues. An m(1)acp(3)Ψ knockout model and hypo-m(1)acp(3)Ψ patient tumors share a translational signature characterized by highly abundant ribosomal proteins. Thus, m(1)acp(3)Ψ-deficient rRNA forms an uncharacterized class of "onco-ribosome" which may serve as a chemotherapeutic target for treating cancer patients

Insights into the Cepheid distance scale

We present an investigation of Cepheid distances using theory and observations. Cepheid models indicate that the slope of the Period-Luminosity (P-L) relation covering the entire period range (0.40<= logP <=2.0) becomes steeper when moving from optical to NIR bands, and that the metallicity dependence of the slope decreases from the B- to the K-band. We estimated V- and I-band slopes for 87 Cepheid data sets belonging to 48 external galaxies with nebular oxygen abundance 7.5<= 12+log (O/H) <=8.9. By using Cepheid samples including more than 20 Cepheids, the chi^2 test indicates that the hypothesis of a steepening of the P-L_{V,I} relations with increased metallicity can be discarded at the 99% level. On the contrary, the observed slopes agree with the metallicity trend predicted by pulsation models, i.e. the slope is roughly constant for galaxies with 12+log (O/H) < 8.17 and becomes shallower in the metal-rich regime, with a confidence level of 62% and 92%, respectively. The chi^2 test concerning the hypothesis that the slope does not depend on metallicity gives confidence levels either similar (P-L_V, 62%) or smaller (P-L_I, 67%). We found that the slopes of optical and NIR Period-Wesenheit (P-W) relations in external galaxies are similar to the slopes of LMC. On this ground, the P-W relations provide robust distances relative to the LMC, but theory and observations indicate that the metallicity dependence of the zero-point in the different passbands has to be taken into account. We compared the galaxy distances provided by Rizzi et al. (2007) using the TRGB with our set of Cepheid distances based on the P-W relations. We found that the metallicity correction on distances based on the P-WBV relation is gamma_(B,V)=-0.52 mag dex^-1, whereas it is vanishing for the distances based on the P-WVI and on the P-WJK relations. These findings fully support Cepheid theoretical predictions.Comment: Paper accepted for publication on ApJ (21 pages, 16 figures)

Trade-off between sex and growth in diatoms: Molecular mechanisms and demographic implications

Diatoms are fast-growing and winning competitors in aquatic environments, possibly due to optimized growth performance. However, their life cycles are complex, heteromorphic, and not fully understood. Here, we report on the fine control of cell growth and physiology during the sexual phase of the marine diatom Pseudo-nitzschia multistriata. We found that mating, under nutrient replete conditions, induces a prolonged growth arrest in parental cells. Transcriptomic analyses revealed down-regulation of genes related to major metabolic functions from the early phases of mating. Single-cell photophysiology also pinpointed an inhibition of photosynthesis and storage lipids accumulated in the arrested population, especially in gametes and zygotes. Numerical simulations revealed that growth arrest affects the balance between parental cells and their siblings, possibly favoring the new generation. Thus, in addition to resources availability, life cycle traits contribute to shaping the species ecological niches and must be considered to describe and understand the structure of plankton communities

TRPA1-dependent and -independent activation by commonly used preservatives

Background and purpose: Addition of preservatives ensures microbial stability, especially in multidose containers of parenterally administered pharmaceuticals. These compounds can cause side effects, and particularly at the site of application, might elicit or facilitate pain. TRPA1 is a cation channel expressed in peripheral neurons which contributes to pain and inflammation and is sensitive to many irritants. The most commonly used preservatives, in particular with a focus on parenteral formulations, were investigated for their potential to activate TRPA1.Experimental approach: Sixteen preservatives were screened for mediating calcium influx in human TRPA1-transfected HEK293t cells. Untransfected cells served as control, results were further validated in mouse sensory neurons. In addition, proinflammatory mediators serotonin, histamine and prostaglandin E2 were co-administered to probe a potential sensitisation of preservative-induced TRPA1 activation.Key results: Butylparaben, propylparaben, ethylparaben, bronopol, methylparaben, phenylethyl alcohol and phenol induced a TRPA1-dependent calcium influx in transfected HEK293t cells at concentrations used for preservation. Other preservatives increased calcium within the used concentration ranges, but to a similar degree in untransfected controls. Serotonin, histamine, and prostaglandin enhanced TRPA1 activation of phenylethyl alcohol, bronopol, ethylparaben, propylparaben and butylparaben.Conclusion and implications: Systematic screening of common preservatives applied for parenterally administered drugs resulted in identifying several preservatives with substantial TRPA1 channel activation. This activation was enhanced by the addition of proinflammatory meditators. This allows selecting a preservative without TRPA1 activation, particularly in case of pharmaceuticals that could act proinflammatory

Engineered extracellular vesicle decoy receptor-mediated modulation of the IL6 trans-signalling pathway in muscle

The cytokine interleukin 6 (IL6) is a key mediator of inflammation that contributes to skeletal muscle pathophysiology. IL6 activates target cells by two main mechanisms, the classical and trans-signalling pathways. While classical signalling is associated with the anti-inflammatory activities of the cytokine, the IL6 trans-signalling pathway mediates chronic inflammation and is therefore a target for therapeutic intervention. Extracellular vesicles (EVs) are natural, lipid-bound nanoparticles, with potential as targeted delivery vehicles for therapeutic macromolecules. Here, we engineered EVs to express IL6 signal transducer (IL6ST) decoy receptors to selectively inhibit the IL6 trans-signalling pathway. The potency of the IL6ST decoy receptor EVs was optimized by inclusion of a GCN4 dimerization domain and a peptide sequence derived from syntenin-1 which targets the decoy receptor to EVs. The resulting engineered EVs were able to efficiently inhibit activation of the IL6 trans-signalling pathway in reporter cells, while having no effect on the IL6 classical signalling. IL6ST decoy receptor EVs, were also capable of blocking the IL6 trans-signalling pathway in C2C12 myoblasts and myotubes, thereby inhibiting the phosphorylation of STAT3 and partially reversing the anti-differentiation effects observed when treating cells with IL6/IL6R complexes. Treatment of a Duchenne muscular dystrophy mouse model with IL6ST decoy receptor EVs resulted in a reduction in STAT3 phosphorylation in the quadriceps and gastrocnemius muscles of these mice, thereby demonstrating in vivo activity of the decoy receptor EVs as a potential therapy. Taken together, this study reveals the IL6 trans-signalling pathway as a promising therapeutic target in DMD, and demonstrates the therapeutic potential of IL6ST decoy receptor EVs