UBR2 of the N-end rule pathway is required for chromosome stability via histone ubiquitylation in spermatocytes and somatic cells

The N-end rule pathway is a proteolytic system in which its recognition components (N-recognins) recognize destabilizing N-terminal residues of short-lived proteins as an essential element of specific degrons, called N-degrons. The RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa), conserved domains and substrate specificities to N-degrons. Despite the known function of the N-end rule pathway in degradation of cytosolic proteins, the major phenotype of UBR2-deficient male mice is infertility caused by arrest of spermatocytes at meiotic prophase I. UBR2-deficient spermatocytes are impaired in transcriptional silencing of sex chromosome-linked genes and ubiquitylation of histone H2A. In this study we show that the recruitment of UBR2 to meiotic chromosomes spatiotemporally correlates to the induction of chromatin-associated ubiquitylation, which is significantly impaired in UBR2-deficient spermatocytes. UBR2 functions as a scaffold E3 that promotes HR6B/UbcH2-dependent ubiquitylation of H2A and H2B but not H3 and H4, through a mechanism distinct from typical polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is allosterically activated by dipeptides bearing destabilizing N-terminal residues. Insufficient monoubiquitylation and polyubiquitylation on UBR2-deficient meiotic chromosomes correlate to defects in double strand break (DSB) repair and other meiotic processes, resulting in pachytene arrest at stage IV and apoptosis. Some of these functions of UBR2 are observed in somatic cells, in which UBR2 is a chromatin-binding protein involved in chromatin-associated ubiquitylation upon DNA damage. UBR2-deficient somatic cells show an array of chromosomal abnormalities, including hyperproliferation, chromosome instability, and hypersensitivity to DNA damage-inducing reagents. UBR2-deficient mice enriched in C57 background die upon birth with defects in lung expansion and neural development. Thus, UBR2, known as the recognition component of a major cellular proteolytic system, is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells. © 2012 Kwon et al

Confluent Orthogonal Drawings of Syntax Diagrams

We provide a pipeline for generating syntax diagrams (also called railroad diagrams) from context free grammars. Syntax diagrams are a graphical representation of a context free language, which we formalize abstractly as a set of mutually recursive nondeterministic finite automata and draw by combining elements from the confluent drawing, layered drawing, and smooth orthogonal drawing styles. Within our pipeline we introduce several heuristics that modify the grammar but preserve the language, improving the aesthetics of the final drawing.Comment: GD 201

Ionic liquids for energy, materials, and medicine.

As highlighted by the recent ChemComm web themed issue on ionic liquids, this field continues to develop beyond the concept of interesting new solvents for application in the greening of the chemical industry. Here some current research trends in the field will be discussed which show that ionic liquids research is still aimed squarely at solving major societal issues by taking advantage of new fundamental understanding of the nature of these salts in their low temperature liquid state. This article discusses current research trends in applications of ionic liquids to energy, materials, and medicines to provide some insight into the directions, motivations, challenges, and successes being achieved with ionic liquids today

Determination of phototropism by UV-B radiation

UV-B phototropism in etiolated Arabidopsis seedlings has only been shown recently and needs further exploration. Here we elaborate on how to generate a customized setup with a unilateral UV-B light source, the required plant materials, different growth substrates, and a framework for data analysis

Hominin teeth from the Middle Pleistocene site of Yiyuan, Eastern China

In 1981-1982, some hominin fossils, including a relatively complete skull and seven isolated teeth, were recovered from the Middle Pleistocene site of Yiyuan in Eastern China. In the present study we provide a detailed metric and morphological comparison of the Yiyuan dental sample in order to characterize better the variability of the human populations that inhabited China during the Middle Pleistocene. Aside from taxonomic and phylogenetic questions, the lack of understanding and/or knowledge about the morphological variability of these populations have caused concern about the human versus non-human nature of some of the hominin dental remains found in East Asia during the Early and the Middle Pleistocene. Thus, our study aims to present a detailed description and comparison of the Yiyuan isolated teeth to 1) discuss and support their human nature and 2) to explore their taxonomic affinities with regard to other penecontemporaneous populations from Asia. Our results clearly differentiate the Yiyuan sample from Pongo specimens and support a human attribution for the Yiyuan material. Our analyses also suggest that the Yiyuan teeth form a morphologically coherent group together with samples from Zhoukoudian, Chaoxian and Hexian. They are different from the more derived specimens from Panxian Dadong, suggesting a pattern of biogeographic isolation and different evolutionary trends between northern and southern China during the Middle Pleistocene. In addition, and despite sharing a common morphological bauplan with Homo erectus sensu stricto (s.s.), the Yiyuan, Zhoukoudian and Hexian teeth are also different from the Indonesian Early Pleistocene samples. In particular, the expression of a highly crenulated or dendritic enamel-dentine surface could be unique to these groups. Our study supports the notion that the taxonomy of the Pleistocene hominins from Asia may have been oversimplified. Future studies should explore the variability of the Asian specimens and reconsider whether all the samples can be attributed to H. erectus s.s

Counterfactual thinking in cooperation dynamics

Counterfactual Thinking is a human cognitive ability studied in a wide variety of domains. It captures the process of reasoning about a past event that did not occur, namely what would have happened had this event occurred, or, otherwise, to reason about an event that did occur but what would ensue had it not. Given the wide cognitive empowerment of counterfactual reasoning in the human individual, the question arises of how the presence of individuals with this capability may improve cooperation in populations of self-regarding individuals. Here we propose a mathematical model, grounded on Evolutionary Game Theory, to examine the population dynamics emerging from the interplay between counterfactual thinking and social learning (i.e., individuals that learn from the actions and success of others) whenever the individuals in the population face a collective dilemma. Our results suggest that counterfactual reasoning fosters coordination in collective action problems occurring in large populations, and has a limited impact on cooperation dilemmas in which coordination is not required. Moreover, we show that a small prevalence of individuals resorting to counterfactual thinking is enough to nudge an entire population towards highly cooperative standards.Comment: 18 page

Pure Samples of Quark and Gluon Jets at the LHC

Having pure samples of quark and gluon jets would greatly facilitate the study of jet properties and substructure, with many potential standard model and new physics applications. To this end, we consider multijet and jets+X samples, to determine the purity that can be achieved by simple kinematic cuts leaving reasonable production cross sections. We find, for example, that at the 7 TeV LHC, the pp {\to} {\gamma}+2jets sample can provide 98% pure quark jets with 200 GeV of transverse momentum and a cross section of 5 pb. To get 10 pb of 200 GeV jets with 90% gluon purity, the pp {\to} 3jets sample can be used. b+2jets is also useful for gluons, but only if the b-tagging is very efficient.Comment: 19 pages, 16 figures; v2 section on formally defining quark and gluon jets has been adde

Heavy Squarks at the LHC

The LHC, with its seven-fold increase in energy over the Tevatron, is capable of probing regions of SUSY parameter space exhibiting qualitatively new collider phenomenology. Here we investigate one such region in which first generation squarks are very heavy compared to the other superpartners. We find that the production of these squarks, which is dominantly associative, only becomes rate-limited at mSquark > 4(5) TeV for L~10(100) fb-1. However, discovery of this scenario is complicated because heavy squarks decay primarily into a jet and boosted gluino, yielding a dijet-like topology with missing energy (MET) pointing along the direction of the second hardest jet. The result is that many signal events are removed by standard jet/MET anti-alignment cuts designed to guard against jet mismeasurement errors. We suggest replacing these anti-alignment cuts with a measurement of jet substructure that can significantly extend the reach of this channel while still removing much of the background. We study a selection of benchmark points in detail, demonstrating that mSquark= 4(5) TeV first generation squarks can be discovered at the LHC with L~10(100)fb-1

Strong Double Higgs Production at the LHC

The hierarchy problem and the electroweak data, together, provide a plausible motivation for considering a light Higgs emerging as a pseudo-Goldstone boson from a strongly-coupled sector. In that scenario, the rates for Higgs production and decay differ significantly from those in the Standard Model. However, one genuine strong coupling signature is the growth with energy of the scattering amplitudes among the Goldstone bosons, the longitudinally polarized vector bosons as well as the Higgs boson itself. The rate for double Higgs production in vector boson fusion is thus enhanced with respect to its negligible rate in the SM. We study that reaction in pp collisions, where the production of two Higgs bosons at high pT is associated with the emission of two forward jets. We concentrate on the decay mode hh -> WW^(*)WW^(*) and study the semi-leptonic decay chains of the W's with 2, 3 or 4 leptons in the final states. While the 3 lepton final states are the most relevant and can lead to a 3 sigma signal significance with 300 fb^{-1} collected at a 14 TeV LHC, the two same-sign lepton final states provide complementary information. We also comment on the prospects for improving the detectability of double Higgs production at the foreseen LHC energy and luminosity upgrades.Comment: 54 pages, 26 figures. v2: typos corrected, a few comments and one table added. Version published in JHE