Mol. Cell. Proteomics

Post-translational modification of proteins by ubiquitin is a fundamentally important regulatory mechanism. However, proteome-wide analysis of endogenous ubiquitylation remains a challenging task, and almost always has relied on cells expressing affinity tagged ubiquitin. Here we combine single-step immunoenrichment of ubiquitylated peptides with peptide fractionation and high-resolution mass spectrometry to investigate endogenous ubiquitylation sites. We precisely map 11,054 endogenous putative ubiquitylation sites (diglycine-modified lysines) on 4,273 human proteins. The presented data set covers 67% of the known ubiquitylation sites and contains 10,254 novel sites on proteins with diverse cellular functions including cell signaling, receptor endocytosis, DNA replication, DNA damage repair, and cell cycle progression. Our method enables site-specific quantification of ubiquitylation in response to cellular perturbations and is applicable to any cell type or tissue. Global quantification of ubiquitylation in cells treated with the proteasome inhibitor MG-132 discovers sites that are involved in proteasomal degradation, and suggests a nonproteasomal function for almost half of all sites. Surprisingly, ubiquitylation of about 15% of sites decreased more than twofold within four hours of MG-132 treatment, showing that inhibition of proteasomal function can dramatically reduce ubiquitylation on many sites with non-proteasomal functions. Comparison of ubiquitylation sites with acetylation sites reveals an extensive overlap between the lysine residues targeted by these two modifications. However, the crosstalk between these two post-translational modifications is significantly less frequent on sites that show increased ubiquitylation upon proteasome inhibition. Taken together, we report the largest site-specific ubiquitylation dataset in human cells, and for the first time demonstrate proteome-wide, site-specific quantification of endogenous putative ubiquitylation sites

Magnetic and electronic structures of superconducting RuSr2_2GdCu2_2O8_8

The coexistence of ferromagnetism and superconductivity in RuSr$_2$GdCu$_2$O$_8$ was reported both from experiments (by Tallon et. al.) and first-principles calculations (by Pickett et. al.). Here we report that our first-principles full-potential linearized augmented plane wave (FLAPW) calculations, employing the precise crystal structure with structural distortions (i.e., RuO$_6$ rotations) determined by neutron diffraction, demonstrate that antiferromagnetic ordering of the Ru moments is energetically favored over the previously proposed ferromagnetic ordering. Our results are consistent with recently performed magnetic neutron diffraction experiments (Lynn et. al). Ru $t_{2g}$ states, which are responsible for the magnetism, have only a very small interaction with Cu $e_g$ states, which results in a small exchange splitting of these states. The Fermi surface, characterized by strongly hybridized $dp\sigma$ orbitals, has nesting features similar to those in the two-dimensional high $T_c$ cuprate superconductors.Comment: 6 pages,6 figures, accepted for publication in Phys. Rev.

Electronic Structure and Charge Dynamics of Huesler Alloy Fe2TiSn Probed by Infrared and Optical Spectroscopy

We report on the electrodynamics of a Heusler alloy Fe2TiSn probed over four decades in energy: from the far infrared to the ultraviolet. Our results do not support the suggestion of Kondo-lattice behavior inferred from specific heat measurements. Instead, we find a conventional Drude-like response of free carriers, with two additional absorption bands centered at around 0.1 and 0.87 eV. The latter feature can be interpreted as excitations across a pseudogap, in accord with band structure calculations.Comment: 3 pages, 4 figure

Surface relaxation and ferromagnetism of Rh(001)

The significant discrepancy between first-principles calculations and experimental analyses for the relaxation of the (001) surface of rhodium has been a puzzle for some years. In this paper we present density functional theory calculations using the local-density approximation and the generalized gradient approximation of the exchange-correlation functional. We investigate the thermal expansion of the surface and the possibility of surface magnetism. The results throw light on several, hitherto overlooked, aspects of metal surfaces. We find, that, when the free energy is considered, density-functional theory provides results in good agreement with experiments.Comment: 6 pages, 4 figures, submitted to Phys. Rev. Lett. (April 28, 1996

Drosophila melanogaster MNK/Chk2 and p53 regulate multiple DNA repair and apoptotic pathways following DNA damage

We have used genetic and microarray analysis to determine how ionizing radiation (IR) induces p53-dependent transcription and apoptosis in Drosophila melanogaster. IR induces MNK/Chk2-dependent phosphorylation of p53 without changing p53 protein levels, indicating that p53 activity can be regulated without an Mdm2-like activity. In a genome-wide analysis of IR-induced transcription in wild-type and mutant embryos, all IR-induced increases in transcript levels required both p53 and the Drosophila Chk2 homolog MNK. Proapoptotic targets of p53 include hid, reaper, sickle, and the tumor necrosis factor family member EIGER: Overexpression of Eiger is sufficient to induce apoptosis, but mutations in Eiger do not block IR-induced apoptosis. Animals heterozygous for deletions that span the reaper, sickle, and hid genes exhibited reduced IR-dependent apoptosis, indicating that this gene complex is haploinsufficient for induction of apoptosis. Among the genes in this region, hid plays a central, dosage-sensitive role in IR-induced apoptosis. p53 and MNK/Chk2 also regulate DNA repair genes, including two components of the nonhomologous end-joining repair pathway, Ku70 and Ku80. Our results indicate that MNK/Chk2-dependent modification of Drosophila p53 activates a global transcriptional response to DNA damage that induces error-prone DNA repair as well as intrinsic and extrinsic apoptosis pathways

Atomic-scale representation and statistical learning of tensorial properties

This chapter discusses the importance of incorporating three-dimensional symmetries in the context of statistical learning models geared towards the interpolation of the tensorial properties of atomic-scale structures. We focus on Gaussian process regression, and in particular on the construction of structural representations, and the associated kernel functions, that are endowed with the geometric covariance properties compatible with those of the learning targets. We summarize the general formulation of such a symmetry-adapted Gaussian process regression model, and how it can be implemented based on a scheme that generalizes the popular smooth overlap of atomic positions representation. We give examples of the performance of this framework when learning the polarizability and the ground-state electron density of a molecule

The PANDA GEM-based TPC Prototype

We report on the development of a GEM-based TPC prototype for the PANDA experiment. The design and requirements of this device will be illustrated, with particular emphasis on the properties of the recently tested GEM-detector, the characterization of the read-out electronics and the development of the tracking software that allows to evaluate the GEM-TPC data.Comment: submitted to NIMA 4 pages, 6 picture

Update on Streptococcus suis research and prevention in the era of antimicrobial restriction: 4th International Workshop on S. suis

Streptococcus suis is a swine pathogen and a zoonotic agent afflicting people in close contact with infected pigs or pork meat. Sporadic cases of human infections have been reported worldwide. In addition, S. suis outbreaks emerged in Asia, making this bacterium a primary health concern in this part of the globe. In pigs, S. suis disease results in decreased performance and increased mortality, which have a significant economic impact on swine production worldwide. Facing the new regulations in preventive use of antimicrobials in livestock and lack of effective vaccines, control of S. suis infections is worrisome. Increasing and sharing of knowledge on this pathogen is of utmost importance. As such, the pathogenesis and epidemiology of the infection, antimicrobial resistance, progress on diagnosis, prevention, and control were among the topics discussed during the 4th International Workshop on Streptococcus suis (held in Montreal, Canada, June 2019). This review gathers together recent findings on this important pathogen from lectures performed by lead researchers from several countries including Australia, Canada, France, Germany, Japan, Spain, Thailand, The Netherlands, UK, and USA. Finally, policies and recommendations for the manufacture, quality control, and use of inactivated autogenous vaccines are addressed to advance this important field in veterinary medicine