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A very precise measurement of the magnetic moment of a single electron bound to a carbon nucleus, combined with a state-of-the-art calculation in the framework of bound-state quantum electrodynamics, gives a new value of the atomic mass of the electron that is more precise than the currently accepted one by a factor of 13. Electron mass to unprecedented precision The atomic mass of the electron is a key parameter for fundamental physics. A precise determination is a challenge because the mass is so low. Sven Sturm and colleagues report on a new determination of the electron's mass in atomic units. The authors measured the magnetic moment of a single electron bound to a reference ion (a bare nucleus of carbon-12). The results were analysed using state-of-the-art quantum electrodynamics theory to yield a mass value with a precision that exceeds the current literature value by more than an order of magnitude. The quest for the value of the electron’s atomic mass has been the subject of continuing efforts over the past few decades 1 , 2 , 3 , 4 . Among the seemingly fundamental constants that parameterize the Standard Model of physics 5 and which are thus responsible for its predictive power, the electron mass m e is prominent, being responsible for the structure and properties of atoms and molecules. It is closely linked to other fundamental constants, such as the Rydberg constant R ∞ and the fine-structure constant α (ref. 6 ). However, the low mass of the electron considerably complicates its precise determination. Here we combine a very precise measurement of the magnetic moment of a single electron bound to a carbon nucleus with a state-of-the-art calculation in the framework of bound-state quantum electrodynamics. The precision of the resulting value for the atomic mass of the electron surpasses the current literature value of the Committee on Data for Science and Technology (CODATA 6 ) by a factor of 13. This result lays the foundation for future fundamental physics experiments 7 , 8 and precision tests of the Standard Model 9 , 10 , 11 .

In mixed systems of trapped ions and cold atoms, the ions and atoms can coexist at different temperatures. This is primarily due to their different trapping and cooling mechanisms. The key questions of how ions can cool collisionally with cold atoms and whether the combined system allows stable coexistence, need to be answered. Here we experimentally demonstrate that rubidium ions cool in contact with magneto-optically trapped rubidium atoms, contrary to the general experimental expectation of ion heating. The cooling process is explained theoretically and substantiated with numerical simulations, which include resonant charge exchange collisions. The mechanism of single collision swap cooling of ions with atoms is discussed. Finally, it is experimentally and numerically demonstrated that the combined ion–atom system is intrinsically stable, which is critical for future cold chemistry experiments with such systems. Trapped ions and atoms coexist at different temperatures in mixed systems, and cooling of ions through collisions with atoms is required for the mixture to stabilize. Ravi et al . study these effects using rubidium atoms and ions, and find a collisional cooling mechanism leading to stability of the mixture.

Target of rapamycin (TOR) kinase is a conserved regulator of cell growth whose activity is modulated in response to nutrients, energy and stress. Key proteins involved in the pathway are conserved in the model photosynthetic microalga Chlamydomonas reinhardtii, but the substrates of TOR kinase and downstream signaling network have not been elucidated. Our study provides a new resource for investigating the phosphorylation networks governed by the TOR kinase pathway in Chlamydomonas. We used quantitative phosphoproteomics to investigate the effects of inhibiting Chlamydomonas TOR kinase on dynamic protein phosphorylation. Wild-type and AZD-insensitive Chlamydomonas strains were treated with TOR-specific chemical inhibitors (rapamycin, AZD8055 and Torin1), after which differentially affected phosphosites were identified. Our quantitative phosphoproteomic dataset comprised 2547 unique phosphosites from 1432 different proteins. Inhibition of TOR kinase caused significant quantitative changes in phosphorylation at 258 phosphosites, from 219 unique phosphopeptides. Our results include Chlamydomonas homologs of TOR signaling-related proteins, including a site on RPS6 with a decrease in phosphorylation. Additionally, phosphosites on proteins involved in translation and carotenoid biosynthesis were identified. Follow-up experiments guided by these phosphoproteomic findings in lycopene beta/epsilon cyclase showed that carotenoid levels are affected by TORC1 inhibition and carotenoid production is under TOR control in algae.

Plasmacytoid dendritic cells [pDCs] represent a rare innate immune subset uniquely endowed with the capacity to produce substantial amounts of type-I interferons. This function of pDCs is critical for effective antiviral defenses and has been implicated in autoimmunity. While IFN-I and select cytokines have been recognized as pDC secreted products, a comprehensive agnostic profiling of the pDC secretome in response to a physiologic stimulus has not been reported. We applied LC-MS/MS to catalogue the repertoire of proteins secreted by pDCs in the unperturbed condition and in response to challenge with influenza H1N1. We report the identification of a baseline pDC secretome, and the repertoire of virus-induced proteins including most type-I interferons, various cytokines, chemokines and granzyme B. Additionally, using single-cell RNA-seq [scRNA-seq], we perform multidimensional analyses of pDC transcriptional diversity immediately ex vivo and following stimulation. Our data evidence preexisting pDC heterogeneity, with subsequent highly specialized roles within the pDC population upon stimulation ranging from dedicated cytokine super-producers to cells with APC-like traits. Dynamic expression of transcription factors and surface markers characterize subclusters within activated pDCs. Integrating the proteomic and transcriptomic datasets confirms the pDC-subcluster origin of the proteins identified in the secretome. Our findings represent the most comprehensive molecular characterization of primary human pDCs at baseline, and in response to influenza virus, reported to date.

BI-X, a therapeutic protein under development for the treatment of human ocular disease via intravitreal administration, binds to its therapeutic targets and endogenous albumin in the vitreous humor. A monkey ocular pharmacokinetic (PK) study following BI-X administration was conducted to measure drug and albumin levels in plasma, the vitreous humor, the aqueous humor, and retina tissue at various timepoints post-dose. A comprehensive bioanalytical approach was implemented in support of this study. Five immunocapture-LC-MS/MS assays were developed and qualified for quantitating BI-X in different matrices, while ELISA was used for albumin measurement. Immunocapture at the protein or peptide level was evaluated to achieve adequate assay sensitivity. Drug and albumin assays were applied for the analysis of the monkey study samples.

Photosynthetic organisms use dynamic post-translational modifications to survive and adapt, which include reversible oxidative modifications of protein thiols that regulate protein structure, function, and activity. Efforts to quantify thiol modifications on a global scale have relied upon peptide derivatization, typically using isobaric tags such as TMT, ICAT, or iTRAQ that are more expensive, less accurate, and provide less proteome coverage than label-free approaches—suggesting the need for improved experimental designs for studies requiring maximal coverage and precision. Herein, we present the coverage and precision of resin-assisted thiol enrichment coupled to label-free quantitation for the characterization of reversible oxidative modifications on protein thiols. Using C. reinhardtii and Arabidopsis as model systems for algae and plants, we quantified 3662 and 1641 unique cysteinyl peptides, respectively, with median coefficient of variation (CV) of 13% and 16%. Further, our method is extendable for the detection of protein abundance changes and stoichiometries of cysteine oxidation. Finally, we demonstrate proof-of-principle for our method, and reveal that exogenous hydrogen peroxide treatment regulates the C. reinhardtii redox proteome by increasing or decreasing the level of oxidation of 501 or 67 peptides, respectively. As protein activity and function is controlled by oxidative modifications on protein thiols, resin-assisted thiol enrichment coupled to label-free quantitation can reveal how intracellular and environmental stimuli affect plant survival and fitness through oxidative stress. Graphical Abstract ᅟ

High-precision measurements of the magnetic moment of the electron bound in hydrogen-and lithium-like ions can be used to test bound-state quantum electrodynamical calculations. In the past measurements with relative experimental uncertainties as low as 2×10-9 were performed on hydrogen-like carbon and oxygen ions. In the current experiment we plan to measure the g-factor of hydrogen-like and lithium-like calcium ions. A relative uncertainty δg/g in the order of 10-9 is aspired. Here, we will give the motivation for the experiment, present the experimental techniques and first results.

▪ Abstract  Properties of charged particles confined in ion traps can be determined to high accuracy. The ability to capture stable and unstable isotopes in such traps with high efficiency has led to a series of measurements of gross properties of nuclei. These recent high-accuracy measurements, along with the enabling technological developments and propects for the field, are presented.

BOUND-state quantum electrodynamical calculations can be tested by high precision measurements of the magnetic moment of the electron bound in hydrogen-like and lithium-like ions. Measurements of hydrogen-like carbon and oxygen achieved relative experimental uncertainties as low as 2 × 10−9. In the current experiment we plan to measure the g-factor of hydrogen-like and lithium-like calcium ions. The aim is to reach a relative uncertainty g/gin the order of 10−9. Here, we will give the motivation for the experiment, present the experimental techniques and the status of the experiment.

Post-translational modifications (PTMs) on proteins to form functional protein products are a key level of cellular signaling regulation. Because of this, there has been an immense effort in the proteomics community to improve quantitative enrichment, acquisition, and bioinformatics strategies for the analysis of PTMs to probe metabolic pathways. The identification of dynamic protein phosphorylation events, a vital PTM, is especially important for understanding kinase/ phosphatase-regulated signaling pathways, and is the focus of this dissertation. The aim of this dissertation is to develop and apply phosphoproteomic strategies in the alga Chlamydomonas reinhardtii to characterize the role of protein phosphorylation on cellular regulation in a diverse array of signaling networks. Techniques for algal cell culturing, protein extraction, quantitative enrichment, acquisition and bioinformatics processing developed and adapted for Chlamydomonas are discussed (Chapter 2). Using these techniques, a quantitative workflow for a dual enrichment strategy to target intact protein kinases via capture on immobilized multiplexed inhibitor beads with subsequent proteolytic digestion of unbound proteins and peptide-based phosphorylation enrichment was developed (Chapter 3). This workflow obtained quantitative coverage on 115 protein kinases and 2,304 phosphopeptides. Application of the quantitative phosphoproteomic pipeline was employed to study the effect of Target of Rapamycin (TOR) kinase inhibition on the Chlamydomonas phosphoproteome in wild-type (Chapter 4) and extension into a rapamycin hypersensitive mutant line (Chapter 5). From the wild-type study, three TOR inhibitors with varying mechanisms of inhibition were used to obtain quantitative coverage on 2,547 unique phosphosites with 258 phosphosites differentially changing following inhibition. This approach identified Chlamydomonas homologs of TOR signaling-related proteins such as RPS6 and LARP1 that had decreased phosphorylation upon TORC1 inhibition. Additionally, this led to follow-up experiments guided by our phosphoproteomic findings showing that carotenoid levels are affected by TORC1 inhibition, the first evidence that carotenoid production is under TOR control. From the rapamycin hypersensitive mutant study, the workflow obtained quantitative coverage on 2,699 phosphosites with 316 sites changing following rapamycin treatment. This study showed similarities with the sites modulated in the wild-type study described in Chapter 4 while also providing another distinct group of phosphosites not previously interrogated.