Strategic implications of counter-geoengineering: clash or cooperation?

Solar geoengineering has received increasing attention as an option to temporarily stabilize global temperatures. A key concern is that heterogeneous preferences over the optimal amount of cooling combined with low deployment costs may allow the country with the strongest incentive for cooling, the so-called free-driver, to impose a substantial externality on the rest of the world. We analyze whether the threat of counter-geoengineering technologies capable of negating the climatic effects of solar geoengineering can overcome the free-driver problem and tilt the game in favour of international cooperation. Our game-theoretical model of countries with asymmetric preferences allows for a rigorous analysis of the strategic interaction surrounding solar geoengineering and counter-geoengineering. We find that counter-geoengineering prevents the free-driver outcome, but not always with benign effects. The presence of counter-geoengineering leads to either a climate clash where countries engage in a non-cooperative escalation of opposing climate interventions (negative welfare effect), a moratorium treaty where countries commit to abstain from either type of climate intervention (indeterminate welfare effect), or cooperative deployment of solar geoengineering (positive welfare effect). We show that the outcome depends crucially on the degree of asymmetry in temperature preferences between countries

COMPARATIVE ANALYSIS OF THE DISCORDANCE BETWEEN THE GLOBAL TRANSCRIPTIONAL AND PROTEOMIC RESPONSE OF THE YEAST SACCHAROMYCES CEREVISIAE TO DELETION OF THE F-BOX PROTEIN, GRR1

Indiana University-Purdue University Indianapolis (IUPUI)The Grr1 (Glucose Repression Resistant) protein in Saccharomyces cerevisiae is an F-box protein for the E3 ubiquitin ligase protein complex known as the SCFGrr1 (Skp, Cullin, F-box). F-box proteins serve as substrate receptors for this complex and in this capacity Grr1 serves to promote the ubiquitylation and subsequent proteasomal degradation of a number of intracellular protein substrates. Substrates of SCFGrr1 include the G1-S phase cyclins, Cln1 and Cln2, the Cdc42 effectors and cell polarity proteins, Gic1 and Gic2, the FCH-bar domain protein, Hof1, required for cytokinesis, the meiosis activating serine/threonine protein kinase, Ime2, the transcriptional regulators of glucose transporters, Mth1 and Std1, and the mitochondrial retrograde response inhibitor Mks1. Stabilization of these substrates lead to pleiotrophic phenotypic defects in grr1Δ strains including resistance to glucose repression, accumulation of grr1Δ cells in G2 and M phase of the cell cycle, sensitivity to osmotic stress, and resistance to divalent cations. However, many of these phenotypes are not reflected at the gene expression level. We conducted a quantitative genomic vii and proteomic comparison of 914 loci in a grr1Δ and wild-type strain grown to early log-phase in glucose media. These loci encompassed 16.7% of the Saccharomyces proteome of which 22.3% exhibited discordance between gene and protein expression. GO process enrichment analysis revealed that discordant loci were enriched in the processes of “trafficking”, “mitosis”, and “carbon/energy” metabolism. Here we show that these instances of discordance are biologically relevant and in fact reflect phenotypes of grr1Δ strains not evident at the transcriptional level. Additionally, through combined biochemical and network analysis of discordant loci among “carbon and energy metabolism” we were able to not only construct a model for central carbon metabolism in grr1Δ strains but also were able to elucidate a novel molecular event that may serve to regulate glucose repression of genes needed for respiration in response to changes in glucose concentration

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Immune activation is essential for the antitumor activity of EZH2 inhibition in urothelial carcinoma

The long-term survival of patients with advanced urothelial carcinoma (UCa) is limited because of innate resistance to treatment. We identified elevated expression of the histone methyltransferase EZH2 as a hallmark of aggressive UCa and hypothesized that EZH2 inhibition, via a small-molecule catalytic inhibitor, might have antitumor effects in UCa. Here, in a carcinogen-induced mouse bladder cancer model, a reduction in tumor progression and an increase in immune infiltration upon EZH2 inhibition were observed. Treatment of mice with EZH2i causes an increase in MHC class II expression in the urothelium and can activate infiltrating T cells. Unexpectedly, we found that the lack of an intact adaptive immune system completely abolishes the antitumor effects induced by EZH2 catalytic inhibition. These findings show that immune evasion is the only important determinant for the efficacy of EZH2 catalytic inhibition treatment in a UCa model

Search for CPCP violation in D0^0→\to KS0^0_\mathrm{S}KS0^0_\mathrm{S} decays in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search is reported for charge-parity D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$$CP$ violation in D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ decays, using data collected in proton-proton collisions at $\sqrt{s}$ = 13 TeV recorded by the CMS experiment in 2018. The analysis uses a dedicated data set that corresponds to an integrated luminosity of 41.6 fb$^{-1}$, which consists of about 10 billion events containing a pair of ẖadrons, nearly all of which decay to charm hadrons. The flavor of the neutral D meson is determined by the pion charge in the reconstructed decays D$^{*+}$$\to$ D$^0\pi^+$ and D$^{*-}$$\to$ D$^0\pi^-$. The D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$$CP$ asymmetry in D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ is measured to be $A_{CP}$( K$^0_\mathrm{S}$K$^0_\mathrm{S}$) = (6.2 $\pm$ 3.0 $\pm$ 0.2 $\pm$ 0.8)%, where the three uncertainties represent the statistical uncertainty, the systematic uncertainty, and the uncertainty in the measurement of the D$^0$ $\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ $CP$ asymmetry in the D$^0$ $\to$ K$^0_\mathrm{S}\pi^+\pi^-$ decay. This is the first D$^0$ $\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ $CP$ asymmetry measurement by CMS in the charm sector as well as the first to utilize a fully hadronic final state