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Protein degradation corrects for imbalanced subunit stoichiometry in OST complex assembly
(2015)Molecular Biology of the CellProtein degradation is essential for cellular homeostasis. We developed a sensitive approach to examining protein degradation rates in Saccharomyces cerevisiae by coupling a SILAC approach to selected reaction monitoring (SRM) mass spectrometry. Combined with genetic tools, this analysis made it possible to study the assembly of the oligosaccharyl transferase complex. The ER-associated degradation machinery compensated for disturbed ...Journal Article -
Spatial distribution of cell-cell and cell-ECM adhesions regulates force balance while maintaining E-cadherin molecular tension in cell pairs
(2015)Molecular Biology of the CellMechanical linkage between cell–cell and cell–extracellular matrix (ECM) adhesions regulates cell shape changes during embryonic development and tissue homoeostasis. We examined how the force balance between cell–cell and cell–ECM adhesions changes with cell spread area and aspect ratio in pairs of MDCK cells. We used ECM micropatterning to drive different cytoskeleton strain energy states and cell-generated traction forces and used a ...Journal Article -
Distinct soil microbial diversity under long-term organic and conventional farming
(2015)The ISME JournalLow-input agricultural systems aim at reducing the use of synthetic fertilizers and pesticides in order to improve sustainable production and ecosystem health. Despite the integral role of the soil microbiome in agricultural production, we still have a limited understanding of the complex response of microbial diversity to organic and conventional farming. Here we report on the structural response of the soil microbiome to more than two ...Journal Article -
Proteasome inhibition and oxidative reactions disrupt cellular homeostasis during heme stress
(2015)Cell Death and DifferentiationDual control of cellular heme levels by extracellular scavenger proteins and degradation by heme oxygenases is essential in diseases associated with increased heme release. During severe hemolysis or rhabdomyolysis, uncontrolled heme exposure can cause acute kidney injury and endothelial cell damage. The toxicity of heme was primarily attributed to its pro-oxidant effects; however additional mechanisms of heme toxicity have not been studied ...Journal Article -
Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity. II. A focus on growth impairment in fish
(2015)ChemosphereAdverse outcome pathways (AOPs) organize knowledge on the progression of toxicity through levels of biological organization. By determining the linkages between toxicity events at different levels, AOPs lay the foundation for mechanism-based alternative testing approaches to hazard assessment. Here, we focus on growth impairment in fish to illustrate the initial stages in the process of AOP development for chronic toxicity outcomes. Growth ...Journal Article -
Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity. I. Challenges and research needs in ecotoxicology
(2015)ChemosphereTo elucidate the effects of chemicals on populations of different species in the environment, efficient testing and modeling approaches are needed that consider multiple stressors and allow reliable extrapolation of responses across species. An adverse outcome pathway (AOP) is a concept that provides a framework for organizing knowledge about the progression of toxicity events across scales of biological organization that lead to adverse ...Journal Article -
The interplay of Hrd3 and the molecular chaperone system ensures efficient degradation of malfolded secretory proteins
(2015)Molecular Biology of the CellMisfolded proteins of the secretory pathway are extracted from the endoplasmic reticulum (ER), polyubiquitylated by a protein complex termed the Hmg-CoA reductase degradation ligase (HRD-ligase), and degraded by cytosolic 26S proteasomes. This process is termed ER-associated protein degradation (ERAD). We previously showed that the membrane protein Der1, which is a subunit of the HRD-ligase, is involved in the export of aberrant polypeptides ...Journal Article -
Epigenetics and proteomics join transcriptomics in the quest for tuberculosis biomarkers
(2015)mBioAn estimated one-third of the world's population is currently latently infected with Mycobacterium tuberculosis. Latent M. tuberculosis infection (LTBI) progresses into active tuberculosis (TB) disease in ~5 to 10% of infected individuals. Diagnostic and prognostic biomarkers to monitor disease progression are urgently needed to ensure better care for TB patients and to decrease the spread of TB. Biomarker development is primarily based ...Journal Article -
Observation of the rare Bs0 →µ+µ− decay from the combined analysis of CMS and LHCb data
(2015)NatureThe standard model of particle physics describes the fundamental particles and their interactions via the strong, electromagnetic and weak forces. It provides precise predictions for measurable quantities that can be tested experimentally. The probabilities, or branching fractions, of the strange B meson ( ) and the B0 meson decaying into two oppositely charged muons (μ+ and μ−) are especially interesting because of their sensitivity to ...Journal Article -
The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease
(2014)Nature BiotechnologyThe domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the 'gold standard' for modeling human influenza virus infection and transmission. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotated 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We ...Journal Article