Regulation of mitosis and taxane response by Daxx and Rassf1

Current theories suggest that mitotic checkpoint proteins are essential for proper cellular response to taxanes, a widely used family of chemotherapeutic compounds. We recently showed that absence or depletion of protein Daxx increases cellular taxol (paclitaxel) resistance-a common trait of patients diagnosed with several malignancies, including breast cancer. Further investigation of Daxxmediated taxol response revealed that Daxx is important for the proper timing of mitosis progression and cyclin B stability. Daxx interacts with mitotic checkpoint protein RAS-association domain family protein 1 (Rassf1) and partially colocalizes with this protein during mitosis. Rassf1/Daxx depletion or expression of Daxx-binding domain of Rassf1 elevates cyclin B stability and increases taxol resistance in cells and mouse xenograft models. In breast cancer patients, we observed the inverse correlation between Daxx and clinical response to taxane-based chemotherapy. These data suggest that Daxx and Rassf1 define a mitotic stress checkpoint that enables cells to exit mitosis as micronucleated cells (and eventually die) when encountered with specific mitotic stress stimuli, including taxol. Surprisingly, depletion of Daxx or Rassf1 does not change the activity of E3 ubiquitin ligase anaphase promotion complex/C in in vitro settings, suggesting the necessity of mitotic cellular environment for proper activation of this checkpoint. Daxx and Rassf1 may become useful predictive markers for the proper selection of patients for taxane chemotherapy

Structural insight into SUMO chain recognition and manipulation by the ubiquitin ligase RNF4

The small ubiquitin-like modifier (SUMO) can form polymeric chains that are important signals in cellular processes such as meiosis, genome maintenance and stress response. The SUMO-targeted ubiquitin ligase RNF4 engages with SUMO chains on linked substrates and catalyses their ubiquitination, which targets substrates for proteasomal degradation. Here we use a segmental labelling approach combined with solution nuclear magnetic resonance (NMR) spectroscopy and biochemical characterization to reveal how RNF4 manipulates the conformation of the SUMO chain, thereby facilitating optimal delivery of the distal SUMO domain for ubiquitin transfer

Pandemic (H1N1) 2009 outbreak on pig farm, Argentina

In June-July 2009, an outbreak of pandemic (H1N1) 2009 infection occurred on a pig farm in Argentina. Molecular analysis indicated that the virus was genetically related to the pandemic (H1N1) 2009 influenza virus strain. The outbreak presumably resulted from direct human-to-pig transmission.Facultad de Ciencias Veterinaria

Pandemic (H1N1) 2009 Outbreak on Pig Farm, Argentina

In June–July 2009, an outbreak of pandemic (H1N1) 2009 infection occurred on a pig farm in Argentina. Molecular analysis indicated that the virus was genetically related to the pandemic (H1N1) 2009 influenza virus strain. The outbreak presumably resulted from direct human-to-pig transmission

A Study of Muon Neutrino Disappearance Using the Fermilab Main Injector Neutrino Beam

We report the results of a search for muon-neutrino disappearance by the Main Injector Neutrino Oscillation Search. The experiment uses two detectors separated by 734 km to observe a beam of neutrinos created by the Neutrinos at the Main Injector facility at Fermi National Accelerator Laboratory. The data were collected in the first 282 days of beam operations and correspond to an exposure of 1.27e20 protons on target. Based on measurements in the Near Detector, in the absence of neutrino oscillations we expected 336 +/- 14 muon-neutrino charged-current interactions at the Far Detector but observed 215. This deficit of events corresponds to a significance of 5.2 standard deviations. The deficit is energy dependent and is consistent with two-flavor neutrino oscillations according to delta m-squared = 2.74e-3 +0.44/-0.26e-3 eV^2 and sin^2(2 theta) > 0.87 at 68% confidence level.Comment: In submission to Phys. Rev.

Measurement of the Atmospheric Muon Charge Ratio at TeV Energies with MINOS

The 5.4 kton MINOS far detector has been taking charge-separated cosmic ray muon data since the beginning of August, 2003 at a depth of 2070 meters-water-equivalent in the Soudan Underground Laboratory, Minnesota, USA. The data with both forward and reversed magnetic field running configurations were combined to minimize systematic errors in the determination of the underground muon charge ratio. When averaged, two independent analyses find the charge ratio underground to be 1.374 +/- 0.004 (stat.) +0.012 -0.010(sys.). Using the map of the Soudan rock overburden, the muon momenta as measured underground were projected to the corresponding values at the surface in the energy range 1-7 TeV. Within this range of energies at the surface, the MINOS data are consistent with the charge ratio being energy independent at the two standard deviation level. When the MINOS results are compared with measurements at lower energies, a clear rise in the charge ratio in the energy range 0.3 -- 1.0 TeV is apparent. A qualitative model shows that the rise is consistent with an increasing contribution of kaon decays to the muon charge ratio.Comment: 16 pages, 17 figure

Wheat-barley hybridization – the last forty years

Abstract Several useful alien gene transfers have been reported from related species into wheat (Triticum aestivum), but very few publications have dealt with the development of wheat/barley (Hordeum vulgare) introgression lines. An overview is given here of wheat 9 barley hybridization over the last forty years, including the development of wheat 9 barley hybrids, and of addition and translocation lines with various barley cultivars. A short summary is also given of the wheat 9 barley hybrids produced with other Hordeum species. The meiotic pairing behaviour of wheat 9 barley hybrids is presented, with special regard to the detection of wheat– barley homoeologous pairing using the molecular cytogenetic technique GISH. The effect of in vitro multiplication on the genome composition of intergeneric hybrids is discussed, and the production and characterization of the latest wheat/barley translocation lines are presented. An overview of the agronomical traits (b-glucan content, earliness, salt tolerance, sprouting resistance, etc.) of the newly developed introgression lines is given. The exploitation and possible use of wheat/barley introgression lines for the most up-to-date molecular genetic studies (transcriptome analysis, sequencing of flow-sorted chromosomes) are also discussed

Measurement of neutrino velocity with the MINOS detectors and NuMI neutrino beam

The velocity of a ~3 GeV neutrino beam is measured by comparing detection times at the near and far detectors of the MINOS experiment, separated by 734 km. A total of 473 far detector neutrino events was used to measure (v-c)/c=5.12.910-5 (at 68% C.L.). By correlating the measured energies of 258 charged-current neutrino events to their arrival times at the far detector, a limit is imposed on the neutrino mass of mnu<50 MeV/c2 (99% C.L.)

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13