Determinants of Initiation Codon Selection during Translation in Mammalian Cells

Factors affecting translation of mRNA contribute to the complexity of eukaryotic proteomes. In some cases, translation of a particular mRNA can generate multiple proteins. However, the factors that determine whether ribosomes initiate translation from the first AUG codon in the transcript, from a downstream codon, or from multiple sites are not completely understood. Various mRNA properties, including AUG codon-accessibility and 5′ leader length have been proposed as potential determinants that affect where ribosomes initiate translation. To explore this issue, we performed studies using synthetic mRNAs with two in-frame AUG codons−both in excellent context. Open reading frames initiating at AUG1 and AUG2 encode large and small isoforms of a reporter protein, respectively. Translation of such an mRNA in COS-7 cells was shown to be 5′ cap-dependent and to occur efficiently from both AUG codons. AUG codon-accessibility was modified by using two different elements: an antisense locked nucleic acid oligonucleotide and an exon-junction complex. When either element was used to mask AUG1, the ratio of the proteins synthesized changed, favoring the smaller (AUG2-initiated) protein. In addition, we observed that increased leader length by itself changed the ratio of the proteins and favored initiation at AUG1. These observations demonstrate that initiation codon selection is affected by various factors, including AUG codon-accessibility and 5′ leader length, and is not necessarily determined by the order of AUG codons (5′→3′). The modulation of AUG codon accessibility may provide a powerful means of translation regulation in eukaryotic cells

Food supplements increase adult tarsus length, but not growth rate, in an island population of house sparrows (Passer domesticus)

<p>Abstract</p> <p>Background</p> <p>Variation in food supply during early development can influence growth rate and body size in many species. However, whilst the detrimental effects of food restriction have often been studied in natural populations, how young individuals respond to an artificial increase in food supply is rarely investigated. Here, we investigated both the short-term and long-term effects of providing house sparrow chicks with food supplements during a key period of growth and development and assessed whether providing food supplements had any persistent effect upon adult size (measured here as tarsus length).</p> <p>Results</p> <p>Male nestlings tended to reach higher mass asymptotes than females. Furthermore, brood size was negatively associated with a chick's asymptotic mass. However, providing food supplements had no influence upon the growth rate or the asymptotic mass of chicks. Adults that received food supplements as chicks were larger, in terms of their tarsus length, than adults that did not receive extra food as chicks. In addition, the variation in tarsus length amongst adult males that were given food supplements as chicks was significantly less than the variance observed amongst males that did not receive food supplements.</p> <p>Conclusions</p> <p>Our results demonstrate that the food supply chicks experience during a critical developmental period can have a permanent effect upon their adult phenotype. Furthermore, providing extra food to chicks resulted in sex-biased variance in a size-related trait amongst adults, which shows that the degree of sexual size dimorphism can be affected by the environment experienced during growth.</p

Simultaneous observations of PKS 2155-304 with H.E.S.S., Fermi, RXTE and ATOM: spectral energy distributions and variability in a low state

We report on the first simultaneous observations that cover the optical, X-ray, and high energy gamma-ray bands of the BL Lac object PKS 2155-304. The gamma-ray bands were observed for 11 days, between 25 August and 6 September 2008, jointly with the Fermi Gamma-ray Space Telescope and the H.E.S.S. atmospheric Cherenkov array, providing the first simultaneous MeV-TeV spectral energy distribution with the new generation of gamma-ray telescopes. The ATOM telescope and the RXTE and Swift observatories provided optical and X-ray coverage of the low-energy component over the same time period. The object was close to the lowest archival X-ray and Very High Energy state, whereas the optical flux was much higher. The light curves show relatively little (~30%$) variability overall when compared to past flaring episodes, but we find a clear optical/VHE correlation and evidence for a correlation of the X-rays with the high energy spectral index. Contrary to previous observations in the flaring state, we do not find any correlation between the X-ray and VHE components. Although synchrotron self-Compton models are often invoked to explain the SEDs of BL Lac objects, the most common versions of these models are at odds with the correlated variability we find in the various bands for PKS 2155-304.Comment: Accepted for publication in the Astrophysical Journa

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Local Governments Expenditures and Spillover Effects - Evidence from Walloon Municipalities

Presentation of preliminary results about local governments expenditures analysis and quantification of spillover effects in Wallonia

Evaluation du critère Externalités du Fonds des communes

Analyse et critique du fonctionnement de la tranche Externalités du Fonds des communes wallon qui n'est pas appropriée pour corriger la défaillance de marché engendrée par les effets de débordement

Optimally-transported generalized method of moments

We propose a novel optimal transport-based version of the Generalized Method of Moment (GMM). Instead of handling overidentified models by reweighting the data until all moment conditions are satisfied (as in Generalized Empirical Likelihood methods), this method proceeds by introducing measurement error of the least mean square magnitude necessary to simultaneously satisfy all moment conditions. This approach, based on the notion of optimal transport, aims to address the problem of assigning a logical interpretation to GMM results even when overidentification tests reject the null, a situation that cannot always be avoided in applications. Our approach thus introduces a practical alternative to standard GMM estimation to circumvent concerns regarding overidentification test rejections

Using spatial modeling to address covariate measurement error

We propose a new estimation methodology to address the presence of covariate measurement error by exploiting the availability of spatial data. The approach uses neighboring observations as repeated measurements, after suitably controlling for the random distance between the observations in a way that allows the use of operator diagonalization methods to establish identification. The method is applicable to general nonlinear models with potentially nonclassical errors and does not rely on a priori distributional assumptions regarding any of the variables. The method's implementation combines a sieve semiparametric maximum likelihood with a first-step kernel conditional density estimator and simulation methods. The method's effectiveness is illustrated through both controlled simulations and an application to the assessment of the effect of pre-colonial political structure on current economic development in Africa