Translation termination depends on the sequential ribosomal entry of eRF1 and eRF3.

Translation termination requires eRF1 and eRF3 for polypeptide-and tRNA-release on stop codons. Additionally, Dbp5/DDX19 and Rli1/ABCE1 are required; however, their function in this process is currently unknown. Using a combination of in vivo and in vitro experiments, we show that they regulate a stepwise assembly of the termination complex. Rli1 and eRF3-GDP associate with the ribosome first. Subsequently, Dbp5-ATP delivers eRF1 to the stop codon and in this way prevents a premature access of eRF3. Dbp5 dissociates upon placing eRF1 through ATP-hydrolysis. This in turn enables eRF1 to contact eRF3, as the binding of Dbp5 and eRF3 to eRF1 is mutually exclusive. Defects in the Dbp5-guided eRF1 delivery lead to premature contact and premature dissociation of eRF1 and eRF3 from the ribosome and to subsequent stop codon readthrough. Thus, the stepwise Dbp5-controlled termination complex assembly is essential for regular translation termination events. Our data furthermore suggest a possible role of Dbp5/DDX19 in alternative translation termination events, such as during stress response or in developmental processes, which classifies the helicase as a potential drug target for nonsense suppression therapy to treat cancer and neurodegenerative diseases

Structural and chemical embrittlement of grain boundaries by impurities: a general theory and first principles calculations for copper

First principles calculations of the Sigma 5 (310)[001] symmetric tilt grain boundary in Cu with Bi, Na, and Ag substitutional impurities provide evidence that in the phenomenon of Bi embrittlement of Cu grain boundaries electronic effects do not play a major role; on the contrary, the embrittlement is mostly a structural or "size" effect. Na is predicted to be nearly as good an embrittler as Bi, whereas Ag does not embrittle the boundary in agreement with experiment. While we reject the prevailing view that "electronic" effects (i.e., charge transfer) are responsible for embrittlement, we do not exclude the role of chemistry. However numerical results show a striking equivalence between the alkali metal Na and the semi metal Bi, small differences being accounted for by their contrasting "size" and "softness" (defined here). In order to separate structural and chemical effects unambiguously if not uniquely, we model the embrittlement process by taking the system of grain boundary and free surfaces through a sequence of precisely defined gedanken processes; each of these representing a putative mechanism. We thereby identify three mechanisms of embrittlement by substitutional impurities, two of which survive in the case of embrittlement or cohesion enhancement by interstitials. Two of the three are purely structural and the third contains both structural and chemical elements that by their very nature cannot be further unravelled. We are able to take the systems we study through each of these stages by explicit computer simulations and assess the contribution of each to the nett reduction in intergranular cohesion. The conclusion we reach is that embrittlement by both Bi and Na is almost exclusively structural in origin; that is, the embrittlement is a size effect.Comment: 13 pages, 5 figures; Accepted in Phys. Rev.

A DZ white dwarf with a 30 MG magnetic field

Magnetic white dwarfs with field strengths below 10 MG are easy to recognize since the Zeeman splitting of spectral lines appears proportional to the magnetic field strength. For fields ≳100 MG, however, transition wavelengths become chaotic, requiring quantum-chemical predictions of wavelengths and oscillator strengths with a non-perturbative treatment of the magnetic field. While highly accurate calculations have previously been performed for hydrogen and helium, the variational techniques employed become computationally intractable for systems with more than three to four electrons. Modern computational techniques, such as finite-field coupled-cluster theory, allow the calculation of many-electron systems in arbitrarily strong magnetic fields. Because around 25 per cent of white dwarfs have metal lines in their spectra, and some of those are also magnetic, the possibility arises for some metals to be observed in very strong magnetic fields, resulting in unrecognizable spectra. We have identified SDSS J114333.48+661531.83 as a magnetic DZ white dwarf, with a spectrum exhibiting many unusually shaped lines at unknown wavelengths. Using atomic data calculated from computational finite-field coupled-cluster methods, we have identified some of these lines arising from Na, Mg, and Ca. Surprisingly, we find a relatively low field strength of 30 MG, where the large number of overlapping lines from different elements make the spectrum challenging to interpret at a much lower field strength than for DAs and DBs. Finally, we model the field structure of SDSS J1143+6615 finding the data are consistent with an offset dipole

ABC Effect in Basic Double-Pionic Fusion --- Observation of a new resonance?

We report on a high-statistics measurement of the basic double pionic fusion reaction $pn \to d\pi^0\pi^0$ over the energy region of the so-called ABC effect, a pronounced low-mass enhancement in the $\pi\pi$-invariant mass spectrum. The measurements were performed with the WASA detector setup at COSY. The data reveal the ABC effect to be associated with a Lorentzian shaped energy dependence in the integral cross section. The observables are consistent with a resonance with $I(J^P) =0(3^+)$ in both $pn$ and $\Delta\Delta$ systems. Necessary further tests of the resonance interpretation are discussed

Detection of autoantibodies against reactive oxygen species modified glutamic acid decarboxylase-65 in type 1 diabetes associated complications

<p>Abstract</p> <p>Background</p> <p>Autoantibodies against glutamate decarboxylase-65 (GAD₆₅Abs) are thought to be a major immunological tool involved in pathogenic autoimmunity development in various diseases. GAD₆₅Abs are a sensitive and specific marker for type 1 diabetes (T1D). These autoantibodies can also be found in 6-10% of patients classified with type 2 diabetes (T2D), as well as in 1-2% of the healthy population. The latter individuals are at low risk of developing T1D because the prevalence rate of GAD₆₅Abs is only about 0.3%. It has, therefore, been suggested that the antibody binding to GAD₆₅in these three different GAD₆₅Ab-positive phenotypes differ with respect to epitope specificity. The specificity of reactive oxygen species modified GAD₆₅(ROS-GAD₆₅) is already well established in the T1D. However, its association in secondary complications of T1D has not yet been ascertained. Hence this study focuses on identification of autoantibodies against ROS-GAD₆₅(ROS-GAD₆₅Abs) and quantitative assays in T1D associated complications.</p> <p>Results</p> <p>From the cohort of samples, serum autoantibodies from T1D retinopathic and nephropathic patients showed high recognition of ROS-GAD₆₅as compared to native GAD₆₅(N-GAD₆₅). Uncomplicated T1D subjects also exhibited reactivity towards ROS-GAD₆₅. However, this was found to be less as compared to the binding recorded from complicated subjects. These results were further proven by competitive ELISA estimations. The apparent association constants (AAC) indicate greater affinity of IgG from retinopathic T1D patients (1.90 × 10^-6M) followed by nephropathic (1.81 × 10^-6M) and uncomplicated (3.11 × 10^-7M) T1D patients for ROS-GAD₆₅compared to N-GAD₆₅.</p> <p>Conclusion</p> <p>Increased oxidative stress and blood glucose levels with extended duration of disease in complicated T1D could be responsible for the gradual formation and/or exposing cryptic epitopes on GAD₆₅that induce increased production of ROS-GAD₆₅Abs. Hence regulation of ROS-GAD₆₅Abs could offer novel tools for analysing and possibly treating T1D complications.</p

Raman spectra and calculated vibrational frequencies of size-selected C16, C18, and C20 clusters

The surface plasmon polariton-enhanced Raman spectra of size-selected C16, C18, and C20 clusters isolated in nitrogen matrices are presented along with the calculated vibrational frequencies for the ring and linear chain isomers. The Raman spectra, recorded at a range of excitation wavelengths from 457.9 to 670 nm, show strong resonance enhancement for the three clusters. The calculated vibrational frequencies for ring and linear chain isomers and the cage and bowl structures for C20 are compared to the experimental frequencies. Systematic shifts in the series of peaks in the 200 cm-1 region for C16, C18, and C20 suggest that the observed isomers have the same geometry, thereby ruling out the bowl and cage isomers for C20. The measured spectra appear to be most consistent with the linear chain isomer. This high-energy isomer may be produced during neutralization of the deposited cluster ions