The Complete Spectrum of Yeast Chromosome Instability Genes Identifies Candidate CIN Cancer Genes and Functional Roles for ASTRA Complex Components

Chromosome instability (CIN) is observed in most solid tumors and is linked to somatic mutations in genome integrity maintenance genes. The spectrum of mutations that cause CIN is only partly known and it is not possible to predict a priori all pathways whose disruption might lead to CIN. To address this issue, we generated a catalogue of CIN genes and pathways by screening ∼2,000 reduction-of-function alleles for 90% of essential genes in Saccharomyces cerevisiae. Integrating this with published CIN phenotypes for other yeast genes generated a systematic CIN gene dataset comprised of 692 genes. Enriched gene ontology terms defined cellular CIN pathways that, together with sequence orthologs, created a list of human CIN candidate genes, which we cross-referenced to published somatic mutation databases revealing hundreds of mutated CIN candidate genes. Characterization of some poorly characterized CIN genes revealed short telomeres in mutants of the ASTRA/TTT components TTI1 and ASA1. High-throughput phenotypic profiling links ASA1 to TTT (Tel2-Tti1-Tti2) complex function and to TORC1 signaling via Tor1p stability, consistent with the role of TTT in PI3-kinase related kinase biogenesis. The comprehensive CIN gene list presented here in principle comprises all conserved eukaryotic genome integrity pathways. Deriving human CIN candidate genes from the list allows direct cross-referencing with tumor mutational data and thus candidate mutations potentially driving CIN in tumors. Overall, the CIN gene spectrum reveals new chromosome biology and will help us to understand CIN phenotypes in human disease

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

A guide to ancient protein studies

Palaeoproteomics is an emerging neologism used to describe the application of mass spectrometry-based approaches to the study of ancient proteomes. As with palaeogenomics (the study of ancient DNA), it intersects evolutionary biology, archaeology and anthropology, with applications ranging from the phylogenetic reconstruction of extinct species to the investigation of past human diets and ancient diseases. However, there is no explicit consensus at present regarding standards for data reporting, data validation measures or the use of suitable contamination controls in ancient protein studies. Additionally, in contrast to the ancient DNA community, no consolidated guidelines have been proposed by which researchers, reviewers and editors can evaluate palaeoproteomics data, in part due to the novelty of the field. Here we present a series of precautions and standards for ancient protein research that can be implemented at each stage of analysis, from sample selection to data interpretation. These guidelines are not intended to impose a narrow or rigid list of authentication criteria, but rather to support good practices in the field and to ensure the generation of robust, reproducible results. As the field grows and methodologies change, so too will best practices. It is therefore essential that researchers continue to provide necessary details on how data were generated and authenticated so that the results can be independently and effectively evaluated. We hope that these proposed standards of practice will help to provide a firm foundation for the establishment of palaeoproteomics as a viable and powerful tool for archaeologists, anthropologists and evolutionary biologists

Measurement of the B+c meson lifetime using B+c→J/ψμ+νμX decays

The lifetime of the $B_c^+$ meson is measured using semileptonic decays having a $J\!/\!\psi$ meson and a muon in the final state. The data, corresponding to an integrated luminosity of $2\mathrm{~fb^{-1}}$, are collected by the LHCb detector in $pp$ collisions at a centre-of-mass energy of $8\,\mathrm{TeV}$. The measured lifetime is $$\tau = 509 \pm 8 \pm 12 \mathrm{~fs},$$ where the first uncertainty is statistical and the second is systematic

Lte1, Cdc14 and MEN-controlled Cdk inactivation in yeast coordinate rDNA decompaction with late telophase progression

The mechanism of chromatin compaction in mitosis has been well studied, while little is known about what controls chromatin decompaction in early G1 phase. We have localized the Condensin subunit Brn1 to a compact spiral of rDNA in mitotic budding yeast cells. Brn1 release and the resulting rDNA decompaction in late telophase coincided with mitotic spindle dissociation, and occurred asymmetrically (daughter cells first). We immunoprecipitated the GTP-exchange factor Lte1, which helps activate the mitotic exit network (MEN) in anaphase, with mitotic Brn1. In lteΔ cells Brn1 release was delayed, even at temperatures that do not impair mitotic exit. Mutations in MEN pathway components that act downstream of Lte1 similarly delayed rDNA decompaction. We found that Brn1 release in wild-type cells coincided with the release of Cdc14 phosphatase from the nucleolus and with mitotic CDK inactivation, yet it could be selectively delayed by perturbation of the MEN pathway. This may argue that different levels of Cdk inactivation control spindle disassembly and chromatin decompaction. Mutation of lte1 also impaired rotation of the nucleus in early G1