1,416 research outputs found

    Mitochondrial RNA editing in Trypanoplasma borreli: new tools, new revelations

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    The kinetoplastids are unicellular flagellates that derive their name from their ‘kinetoplast’, a region within each flagellate’s single mitochondrion harboring its organellar genome of high DNA content. Some protein products of this mitochondrial genome are encoded as cryptogenes; their transcripts require editing to generate an open reading frame. This happens through an RNA editing process, whereby small regulatory guide RNAs direct the proper insertion and deletion of one or more uridines at each editing site within specific transcript regions. An accurate perspective of the mitochondrial DNA expansion of kinetoplastids and the evolution of their unique uridine insertion/deletion editing across the entire group has been difficult to achieve. Here, we resolved outstanding questions about the organization of the mitochondrial genome and its editing in the kinetoplastid Trypanoplasma borreli that is evolutionarily distant from the frequently-studied trypanosomatids. We find that its mitochondrial DNA consists of circular molecules of 42 kb that harbor the rRNA and mRNAs, and 17 different contigs of approximately 70 kb carrying an average of 23 putative guide RNA loci per contig. These contigs may be linear molecules; they contain repetitive termini. Our analysis uncovered a putative gRNA population with unique length and sequence parameters that is massive relative to the editing needs of this parasite. We validated or determined the sequence identity of each of the four edited mRNA species – including one coding for ATP synthase 6 that was previously thought to be missing. We utilized our computational methods to show that the T. borreli transcriptome includes a substantial number of transcripts with editing patterns not consistent with the identified product, a result of non-canonical editing. We also discovered that this species is more likely than other kinetoplastids to utilize uridine deletion to enforce amino acid conservation of cryptogene products, although deletion is still less common than insertion. Finally, in three tested kinetoplastid mitochondrial transcriptomes, uridine deletion is more common in the raw mitochondrial read population than it appears when the fully edited translationally competent mRNAs only are considered. We conclude that the organization of mitochondrial DNA across all kinetoplastids can be described as variations on several central themes. These themes include partitioned coding and repetitive regions of a circular molecule encoding mRNA and rRNA, and guide RNA loci positioned on a malleable population of multiple molecules that differ in relative abundance in different strains. Likewise, while all kinetoplastids possess the central mechanism of uridine insertion/deletion RNA editing, its output parameters are species-specific

    Measuring Invisible Particle Masses Using a Single Short Decay Chain

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    We consider the mass measurement at hadron colliders for a decay chain of two steps, which ends with a missing particle. Such a topology appears as a subprocess of signal events of many new physics models which contain a dark matter candidate. From the two visible particles coming from the decay chain, only one invariant mass combination can be formed and hence it is na\"ively expected that the masses of the three invisible particles in the decay chain cannot be determined from a single end point of the invariant mass distribution. We show that the event distribution in the log⁥(E1T/E2T)\log(E_{1T}/E_{2T}) vs. invariant mass-squared plane, where E1TE_{1T}, E2TE_{2T} are the transverse energies of the two visible particles, contains the information of all three invisible particle masses and allows them to be extracted individually. The experimental smearing and combinatorial issues pose challenges to the mass measurements. However, in many cases the three invisible particle masses in the decay chain can be determined with reasonable accuracies.Comment: 45 pages, 32 figure

    The Interplay Between GUT and Flavour Symmetries in a Pati-Salam x S4 Model

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    Both Grand Unified symmetries and discrete flavour symmetries are appealing ways to describe apparent structures in the gauge and flavour sectors of the Standard Model. Both symmetries put constraints on the high energy behaviour of the theory. This can give rise to unexpected interplay when building models that possess both symmetries. We investigate on the possibility to combine a Pati-Salam model with the discrete flavour symmetry S4S_4 that gives rise to quark-lepton complementarity. Under appropriate assumptions at the GUT scale, the model reproduces fermion masses and mixings both in the quark and in the lepton sectors. We show that in particular the Higgs sector and the running Yukawa couplings are strongly affected by the combined constraints of the Grand Unified and family symmetries. This in turn reduces the phenomenologically viable parameter space, with high energy mass scales confined to a small region and some parameters in the neutrino sector slightly unnatural. In the allowed regions, we can reproduce the quark masses and the CKM matrix. In the lepton sector, we reproduce the charged lepton masses, including bottom-tau unification and the Georgi-Jarlskog relation as well as the two known angles of the PMNS matrix. The neutrino mass spectrum can present a normal or an inverse hierarchy, and only allowing the neutrino parameters to spread into a range of values between λ−2\lambda^{-2} and λ2\lambda^2, with λ≃0.2\lambda\simeq0.2. Finally, our model suggests that the reactor mixing angle is close to its current experimental bound.Comment: 62 pages, 4 figures; references added, version accepted for publication in JHE

    Pathogenomic analyses of Shigella isolates inform factors limiting shigellosis prevention and control across LMICs

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    Shigella spp. are the leading bacterial cause of severe childhood diarrhoea in low- and middle-income countries (LMICs), are increasingly antimicrobial resistant and have no widely available licenced vaccine. We performed genomic analyses of 1,246 systematically collected shigellae sampled from seven countries in sub-Saharan Africa and South Asia as part of the Global Enteric Multicenter Study (GEMS) between 2007 and 2011, to inform control and identify factors that could limit the effectiveness of current approaches. Through contemporaneous comparison among major subgroups, we found that S. sonnei contributes ≥6-fold more disease than other Shigella species relative to its genomic diversity, and highlight existing diversity and adaptative capacity among S. flexneri that may generate vaccine escape variants in <6 months. Furthermore, we show convergent evolution of resistance against ciprofloxacin, the current WHO-recommended antimicrobial for the treatment of shigellosis, among Shigella isolates. This demonstrates the urgent need to integrate existing genomic diversity into vaccine and treatment plans for Shigella, providing a framework for the focused application of comparative genomics to guide vaccine development, and the optimization of control and prevention strategies for other pathogens relevant to public health policy considerations

    Quantitative 3-Dimensional Imaging of Murine Neointimal and Atherosclerotic Lesions by Optical Projection Tomography

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    Traditional methods for the analysis of vascular lesion formation are labour intensive to perform - restricting study to ‘snapshots’ within each vessel. This study was undertaken to determine the suitability of optical projection tomographic (OPT) imaging for the 3-dimensional representation and quantification of intimal lesions in mouse arteries. = 0.85), confirming both the accuracy of this methodology and its non-destructive nature. It was also possible to record volumetric measurements of lesion and lumen and these were highly reproducible between scans (coefficient of variation = 5.36%, 11.39% and 4.79% for wire- and ligation-injury and atherosclerosis, respectively).These data demonstrate the eminent suitability of OPT for imaging of atherosclerotic and neointimal lesion formation, providing a much needed means for the routine 3-dimensional analysis of vascular morphology in studies of this type

    Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

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    A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

    Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV

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    The t t-bar production cross section (sigma[t t-bar]) is measured in proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS experiment, corresponding to an integrated luminosity of 2.3 inverse femtobarns. The measurement is performed in events with two leptons (electrons or muons) in the final state, at least two jets identified as jets originating from b quarks, and the presence of an imbalance in transverse momentum. The measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/- 2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction of the standard model.Comment: Replaced with published version. Included journal reference and DO

    Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

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    A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu

    Combined search for the quarks of a sequential fourth generation

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    Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO
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