Resetting a functional G1 nucleus after mitosis

© The Author(s) 2015. The maintenance of the correct cellular information goes beyond the simple transmission of an intact genetic code from one generation to the next. Epigenetic changes, topological cues and correct protein-protein interactions need to be re-established after each cell division to allow the next cell cycle to resume in the correct regulated manner. This process begins with mitotic exit and re-sets all the changes that occurred during mitosis thus restoring a functional G1 nucleus in preparation for the next cell cycle. Mitotic exit is triggered by inactivation of mitotic kinases and the reversal of their phosphorylation activities on many cellular components, from nuclear lamina to transcription factors and chromatin itself. To reverse all these phosphorylations, phosphatases act during mitotic exit in a timely and spatially controlled manner directing the events that lead to a functional G1 nucleus. In this review, we will summarise the recent developments on the control of phosphatases and their known substrates during mitotic exit, and the key steps that control the restoration of chromatin status, nuclear envelope reassembly and nuclear body re-organisation. Although pivotal work has been conducted in this area in yeast, due to differences between the mitotic exit network between yeast and vertebrates, we will mainly concentrate on the vertebrate system.BBSRC grant (BB/K017632/1)

Thermoelectric spin voltage in graphene

In recent years, new spin-dependent thermal effects have been discovered in ferromagnets, stimulating a growing interest in spin caloritronics, a field that exploits the interaction between spin and heat currents. Amongst the most intriguing phenomena is the spin Seebeck effect, in which a thermal gradient gives rise to spin currents that are detected through the inverse spin Hall effect. Non-magnetic materials such as graphene are also relevant for spin caloritronics, thanks to efficient spin transport, energy-dependent carrier mobility and unique density of states. Here, we propose and demonstrate that a carrier thermal gradient in a graphene lateral spin valve can lead to a large increase of the spin voltage near to the graphene charge neutrality point. Such an increase results from a thermoelectric spin voltage, which is analogous to the voltage in a thermocouple and that can be enhanced by the presence of hot carriers generated by an applied current. These results could prove crucial to drive graphene spintronic devices and, in particular, to sustain pure spin signals with thermal gradients and to tune the remote spin accumulation by varying the spin-injection bias

Human activities link fruit bat presence to Ebola virus disease outbreaks

1. A significant link between forest loss and fragmentation and human outbreaks of Ebola virus disease (EVD) has been documented. Deforestation may alter the natural circulation of viruses as well as change the composition, abundance, behaviour and possibly viral exposure of reservoir species. This in turn might increase contact between infected animals and humans. Fruit bats of the family Pteropodidae have been suspected as reservoirs of the Ebola virus. Though there is no solid proof that fruit bats cause human EVD outbreaks, this group of animals have been intermittently infected with the Ebola virus. 2. Our study investigates whether human activities positively affect African fruit bat species’ ranges and whether their ranges are linked to EVD outbreaks, in turn favoured by deforestation. 3. We use species observation records for the 20 fruit bat species found in Africa to determine factors affecting their distribution in two geographical scenarios: 1) the African continent; and 2) inside the predicted Ebola virus range. We do this by employing a hypothetico-deductive approach based on favourability modelling. 4. Our models point to clear associations between human activities and fruit bat distributions that may help scientists understand the anthropogenic settings that could cause the Ebola virus to jump from animals to humans. 5. We show that fruit bat distributions are linked to human activities throughout Africa and particularly within the region where the Ebola virus occurs. More specifically, the areas where human activities favour the presence of five fruit bat species (four of which had recorded seropositive individuals) overlap with EVD outbreak areas, themselves favoured by deforestation. 6. Our work is a useful first step to further investigate the networks and pathways that may lead to an EVD outbreak. The modelling framework we employ here can be employed for other emerging infectious diseases

Is there a role for glucocorticoid receptor beta in asthma?

Glucocorticoids (GCs) are routinely used as anti-inflammatory drugs in the treatment of asthma. They act through binding to glucocorticoid receptor α (GRα), which represses numerous genes encoding pro-inflammatory mediators. A hormone binding deficient GR isoform named GRβ has been isolated in humans. When overexpressed by transfection, GRβ may function as a dominant negative modulator of GRα. However, to act as such, GRβ has to be more abundant than GRα, and conflicting data have been obtained concerning the relative levels of the two isoforms in cell lines and freshly isolated cells. Moreover, the dominant negative effect was not confirmed by independent laboratories. In GC-resistant asthmatics, GRβ was expressed by an increased number of peripheral blood mononuclear cells (PBMCs), airway T cells, and cells found in skin biopsies of tuberculin responses. However, the relative amounts of GRα and GRβ in these cells were not determined. In GC-dependent asthmatics, PBMCs expressed GRα predominantly. No cells containing higher levels of GRβ than GRα have yet been reported in asthmatics. Even if the existence of such cells is demonstrated, the role of GRβ in asthma will remain a matter of controversy because functional studies have given discrepant data

Diffractive Dijet Production at sqrt(s)=630 and 1800 GeV at the Fermilab Tevatron

We report a measurement of the diffractive structure function $F_{jj}^D$ of the antiproton obtained from a study of dijet events produced in association with a leading antiproton in $\bar pp$ collisions at $\sqrt s=630$ GeV at the Fermilab Tevatron. The ratio of $F_{jj}^D$ at $\sqrt s=630$ GeV to $F_{jj}^D$ obtained from a similar measurement at $\sqrt s=1800$ GeV is compared with expectations from QCD factorization and with theoretical predictions. We also report a measurement of the $\xi$ ($x$-Pomeron) and $\beta$ ($x$ of parton in Pomeron) dependence of $F_{jj}^D$ at $\sqrt s=1800$ GeV. In the region $0.035<\xi<0.095$, $|t|<1$ GeV$^2$ and $\beta<0.5$, $F_{jj}^D(\beta,\xi)$ is found to be of the form $\beta^{-1.0\pm 0.1} \xi^{-0.9\pm 0.1}$, which obeys $\beta$-$\xi$ factorization.Comment: LaTeX, 9 pages, Submitted to Phys. Rev. Letter

A Study of B0 -> J/psi K(*)0 pi+ pi- Decays with the Collider Detector at Fermilab

We report a study of the decays B0 -> J/psi K(*)0 pi+ pi-, which involve the creation of a u u-bar or d d-bar quark pair in addition to a b-bar -> c-bar(c s-bar) decay. The data sample consists of 110 1/pb of p p-bar collisions at sqrt{s} = 1.8 TeV collected by the CDF detector at the Fermilab Tevatron collider during 1992-1995. We measure the branching ratios to be BR(B0 -> J/psi K*0 pi+ pi-) = (8.0 +- 2.2 +- 1.5) * 10^{-4} and BR(B0 -> J/psi K0 pi+ pi-) = (1.1 +- 0.4 +- 0.2) * 10^{-3}. Contributions to these decays are seen from psi(2S) K(*)0, J/psi K0 rho0, J/psi K*+ pi-, and J/psi K1(1270)

HPV16 oncogene expression levels during early cervical carcinogenesis are determined by the balance of epigenetic chromatin modifications at the integrated virus genome.

In cervical squamous cell carcinomas, high-risk human papillomavirus (HRHPV) DNA is usually integrated into host chromosomes. Multiple integration events are thought to be present within the cells of a polyclonal premalignant lesion and the features that underpin clonal selection of one particular integrant remain poorly understood. We previously used the W12 model system to generate a panel of cervical keratinocyte clones, derived from cells of a low-grade premalignant lesion naturally infected with the major HRHPV type, HPV16. The cells were isolated regardless of their selective advantage and differed only by the site of HPV16 integration into the host genome. We used this resource to test the hypothesis that levels of HPV16 E6/E7 oncogene expression in premalignant cells are regulated epigenetically. We performed a comprehensive analysis of the epigenetic landscape of the integrated HPV16 DNA in selected clones, in which levels of virus oncogene expression per DNA template varied ~6.6-fold. Across the cells examined, higher levels of virus expression per template were associated with more open chromatin at the HPV16 long control region, together with greater loading of chromatin remodelling enzymes and lower nucleosome occupancy. There were higher levels of histone post-translational modification hallmarks of transcriptionally active chromatin and lower levels of repressive hallmarks. There was greater abundance of the active/elongating form of the RNA polymerase-II enzyme (RNAPII-Ser2P), together with CDK9, the component of positive transcription elongation factor b complex responsible for Ser2 phosphorylation. The changes observed were functionally significant, as cells with higher HPV16 expression per template showed greater sensitivity to depletion and/or inhibition of histone acetyltransferases and CDK9 and less sensitivity to histone deacetylase inhibition. We conclude that virus gene expression per template following HPV16 integration is determined through multiple layers of epigenetic regulation, which are likely to contribute to selection of individual cells during cervical carcinogenesis.This work was supported by Cancer Research UK (Programme Grant A13080); the Medical Research Council; The Pathological Society of Great Britain and Ireland (E.L.A.K.); and the Agency for Science, Technology and Research, Singapore (Q.Y.A).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/onc.2016.

Precise measurement of the W-boson mass with the CDF II detector

We have measured the W-boson mass MW using data corresponding to 2.2/fb of integrated luminosity collected in proton-antiproton collisions at 1.96 TeV with the CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most precise measurement of the W-boson mass to date and significantly exceeds the precision of all previous measurements combined

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO