RNF40 regulates gene expression in an epigenetic context-dependent manner

Background Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively acting histone modification and that increased H2Bub1 occupancy correlates with increased gene expression. In contrast, depletion of the H2B ubiquitin ligases RNF20 or RNF40 alters the expression of only a subset of genes. Results Using conditional Rnf40 knockout mouse embryo fibroblasts, we show that genes occupied by low to moderate amounts of H2Bub1 are selectively regulated in response to Rnf40 deletion, whereas genes marked by high levels of H2Bub1 are mostly unaffected by Rnf40 loss. Furthermore, we find that decreased expression of RNF40-dependent genes is highly associated with widespread narrowing of H3K4me3 peaks. H2Bub1 promotes the broadening of H3K4me3 to increase transcriptional elongation, which together lead to increased tissue-specific gene transcription. Notably, genes upregulated following Rnf40 deletion, including Foxl2, are enriched for H3K27me3, which is decreased following Rnf40 deletion due to decreased expression of the Ezh2 gene. As a consequence, increased expression of some RNF40-“suppressed” genes is associated with enhancer activation via FOXL2. Conclusion Together these findings reveal the complexity and context-dependency whereby one histone modification can have divergent effects on gene transcription. Furthermore, we show that these effects are dependent upon the activity of other epigenetic regulatory proteins and histone modifications

Quantum Gates and Memory using Microwave Dressed States

Trapped atomic ions have been successfully used for demonstrating basic elements of universal quantum information processing (QIP). Nevertheless, scaling up of these methods and techniques to achieve large scale universal QIP, or more specialized quantum simulations remains challenging. The use of easily controllable and stable microwave sources instead of complex laser systems on the other hand promises to remove obstacles to scalability. Important remaining drawbacks in this approach are the use of magnetic field sensitive states, which shorten coherence times considerably, and the requirement to create large stable magnetic field gradients. Here, we present theoretically a novel approach based on dressing magnetic field sensitive states with microwave fields which addresses both issues and permits fast quantum logic. We experimentally demonstrate basic building blocks of this scheme to show that these dressed states are long-lived and coherence times are increased by more than two orders of magnitude compared to bare magnetic field sensitive states. This changes decisively the prospect of microwave-driven ion trap QIP and offers a new route to extend coherence times for all systems that suffer from magnetic noise such as neutral atoms, NV-centres, quantum dots, or circuit-QED systems.Comment: 9 pages, 4 figure

The state of peer-to-peer network simulators

Networking research often relies on simulation in order to test and evaluate new ideas. An important requirement of this process is that results must be reproducible so that other researchers can replicate, validate and extend existing work. We look at the landscape of simulators for research in peer-to-peer (P2P) networks by conducting a survey of a combined total of over 280 papers from before and after 2007 (the year of the last survey in this area), and comment on the large quantity of research using bespoke, closed-source simulators. We propose a set of criteria that P2P simulators should meet, and poll the P2P research community for their agreement. We aim to drive the community towards performing their experiments on simulators that allow for others to validate their results

Increased S-nitrosylation and proteasomal degradation of caspase-3 during infection contribute to the persistence of adherent invasive escherichia coli (AIEC) in immune cells

Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn's disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

The 2018 biomembrane curvature and remodeling roadmap

The importance of curvature as a structural feature of biological membranes has been recognized for many years and has fascinated scientists from a wide range of different backgrounds. On the one hand, changes in membrane morphology are involved in a plethora of phenomena involving the plasma membrane of eukaryotic cells, including endo-and exocytosis, phagocytosis and filopodia formation. On the other hand, a multitude of intracellular processes at the level of organelles rely on generation, modulation, and maintenance of membrane curvature to maintain the organelle shape and functionality. The contribution of biophysicists and biologists is essential for shedding light on the mechanistic understanding and quantification of these processes. Given the vast complexity of phenomena and mechanisms involved in the coupling between membrane shape and function, it is not always clear in what direction to advance to eventually arrive at an exhaustive understanding of this important research area. The 2018 Biomembrane Curvature and Remodeling Roadmap of Journal of Physics D: Applied Physics addresses this need for clarity and is intended to provide guidance both for students who have just entered the field as well as established scientists who would like to improve their orientation within this fascinating area

Longitudinal double-spin asymmetry for inclusive jet production in p+p collisions at sqrt(s)=200 GeV

We report a new STAR measurement of the longitudinal double-spin asymmetry A_LL for inclusive jet production at mid-rapidity in polarized p+p collisions at a center-of-mass energy of sqrt(s) = 200 GeV. The data, which cover jet transverse momenta 5 < p_T < 30 GeV/c, are substantially more precise than previous measurements. They provide significant new constraints on the gluon spin contribution to the nucleon spin through the comparison to predictions derived from one global fit of polarized deep-inelastic scattering measurements.Comment: 7 pages, 4 figures + 1 tabl

Measurements of ϕ\phi meson production in relativistic heavy-ion collisions at RHIC

We present results for the measurement of $\phi$ meson production via its charged kaon decay channel $\phi \to K^+K^-$ in Au+Au collisions at $\sqrt{s_{_{NN}}}=62.4$, 130, and 200 GeV, and in $p+p$ and $d$+Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV from the STAR experiment at the BNL Relativistic Heavy Ion Collider (RHIC). The midrapidity ($|y|<0.5$) $\phi$ meson transverse momentum ($p_{T}$) spectra in central Au+Au collisions are found to be well described by a single exponential distribution. On the other hand, the $p_{T}$ spectra from $p+p$, $d$+Au and peripheral Au+Au collisions show power-law tails at intermediate and high $p_{T}$ and are described better by Levy distributions. The constant $\phi/K^-$ yield ratio vs beam species, collision centrality and colliding energy is in contradiction with expectations from models having kaon coalescence as the dominant mechanism for $\phi$ production at RHIC. The $\Omega/\phi$ yield ratio as a function of $p_{T}$ is consistent with a model based on the recombination of thermal $s$ quarks up to $p_{T}\sim 4$ GeV/$c$, but disagrees at higher transverse momenta. The measured nuclear modification factor, $R_{dAu}$, for the $\phi$ meson increases above unity at intermediate $p_{T}$, similar to that for pions and protons, while $R_{AA}$ is suppressed due to the energy loss effect in central Au+Au collisions. Number of constituent quark scaling of both $R_{cp}$ and $v_{2}$ for the $\phi$ meson with respect to other hadrons in Au+Au collisions at $\sqrt{s_{_{NN}}}$=200 GeV at intermediate $p_{T}$ is observed. These observations support quark coalescence as being the dominant mechanism of hadronization in the intermediate $p_{T}$ region at RHIC.Comment: 22 pages, 21 figures, 4 table