Strain controlled oxygen vacancy formation and ordering in CaMnO3_3

We use first-principles calculations to investigate the stability of bi-axially strained \textit{Pnma} perovskite CaMnO$_3$ towards the formation of oxygen vacancies. Our motivation is provided by promising indications that novel material properties can be engineered by application of strain through coherent heteroepitaxy in thin films. While it is usually assumed that such epitaxial strain is accommodated primarily by changes in intrinsic lattice constants, point defect formation is also a likely strain relaxation mechanism. This is particularly true at the large strain magnitudes ($>$4%) which first-principles calculations often suggest are required to induce new functionalities. We find a strong dependence of oxygen vacancy defect formation energy on strain, with tensile strain lowering the formation energy consistent with the increasing molar volume with increasing oxygen deficiency. In addition, we find that strain differentiates the formation energy for different lattice sites, suggesting its use as a route to engineering vacancy ordering in epitaxial thin films.Comment: 7 pages, 7 figure

Gene expression: degrade to derepress

Chromatin immunoprecipitation and sequencing (ChIP‐seq) provides a static snap‐shot of DNA‐associated proteins which fails to reflect the dynamics of the DNA‐bound proteome. Now, Catic and co‐workers combine ubiquitin ChIP‐seq and proteasome inhibitors to map sites of DNA‐associated protein degradation on a genome‐wide scale. They identify an ubiquitin ligase which targets a transcriptional repressor for destruction by the proteasome, thus activating transcription of specific genes. These findings reveal that the ubiquitin proteasome system actively regulates transcription

Structural phases driven by oxygen vacancies at the La0.7Sr0.3MnO3/SrTiO3 hetero-interface

An oxygen vacancy driven structural response at the epitaxial interface between La0.7Sr0.3MnO3 films and SrTiO3 substrates is reported. A combined scanning transmission electron microscopy and electron energy loss spectroscopy study reveal the presence of an elongated out-of-plane lattice parameter, coupled to oxygen vacancies and reduced manganese oxidation state at the La0.7Sr0.3MnO3 side of the interface. Density functional theory calculations support that the measured interface structure is a disordered oxygen deficient brownmillerite structure. The effect of oxygen vacancy mobility is assessed, revealing an ordering of the vacancies with time

SILAC for biomarker discovery

Stable isotope labeling in cell culture (SILAC) has been employed in mass spectrometry-based proteomics for nearly a decade. This method is based on cells in culture metabolically incorporating isotope-coded essential amino acids and allows the quantification of global protein populations to identify characteristic changes. Variations of this technique developed over the years allow the application of SILAC not only to cell culture-derived samples but also to tissues and human specimens, making this powerful technique amenable to clinically relevant samples. In this review we provide an overview of different SILAC-derived methods and their use in the identification and development of biomarkers

Systematic errors in peptide and protein identification and quantification by modified peptides

The principle of shotgun proteomics is to use peptide mass spectra in order to identify corresponding sequences in a protein database. The quality of peptide and protein identification and quantification critically depends on the sensitivity and specificity of this assignment process. Many peptides in proteomic samples carry biochemical modifications, and a large fraction of unassigned spectra arise from modified peptides. Spectra derived from modified peptides can erroneously be assigned to wrong amino acid sequences. However, the impact of this problem on proteomic data has not yet been investigated systematically. Here we use combinations of different database searches to show that modified peptides can be responsible for 20-50 % of false positive identifications in deep proteomic datasets. These false positive hits are particularly problematic as they have significantly higher scores and higher intensities than other false positive matches. Furthermore, these wrong peptide assignments lead to hundreds of false protein identifications and systematic biases in protein quantification. We devise a "cleaned search" strategy to address this problem and show that this considerably improves the sensitivity and specificity of proteomic data. In summary, we show that modified peptides cause systematic errors in peptide and protein identification and quantification and should therefore be considered to further improve the quality of proteomic data annotation

Unconventional order-disorder phase transition in improper ferroelectric hexagonal manganites

The improper ferroelectricity in YMnO$_3$ and other related multiferroic hexagonal manganites are known to cause topologically protected ferroelectric domains that give rise to rich and diverse physical phenomena. The local structure and structural coherence across the ferroelectric transition, however, were previously not well understood. Here we reveal the evolution of the local structure with temperature in YMnO$_3$ using neutron total scattering techniques, and interpret them with the help of first-principles calculations. The results show that, at room temperature, the local and average structures are consistent with the established ferroelectric $P6_3cm$ symmetry. On heating, both local and average structural analyses show striking anomalies from $\sim 800$ K up to the Curie temperature consistent with increasing fluctuations of the order parameter angle. These fluctuations result in an unusual local symmetry lowering into a \textit{continuum of structures} on heating. This local symmetry breaking persists into the high-symmetry non-polar phase, constituting an unconventional type of order-disorder transition.Comment: 10 pages, 5 figure

Yos9p assists in the degradation of certain non-glycosylated proteins from the endoplasmic reticulum

The HRD ubiquitin ligase recognizes and ubiquitylates proteins of the endoplasmic reticulum that display structural defects. Here, we apply quantitative proteomics to characterize the substrate spectrum of the HRD complex. Among the identified substrates is Erg3p, a glycoprotein involved in sterol-synthesis. We characterize Erg3p and demonstrate that the elimination of Erg3p requires Htm1p and Yos9p, two proteins that partake in the glycan-dependent turnover of aberrant proteins. We further show that the HRD ligase also mediates the breakdown of Erg3p and CPY* engineered to lack N-glycans. The degradation of these non-glycosylated substrates is enhanced by a mutant variant of Yos9p that has lost its affinity for oligosaccharides, indicating that Yos9p has a previously unrecognized role in the quality control of non-glycosylated proteins