PROSPINO: A Program for the Production of Supersymmetric Particles in Next-to-leading Order QCD

A Fortran-program for the production cross-sections of squarks and gluinos at hadron colliders is described. It includes full next-to-leading order SUSY-QCD corrections to all possible final states (\squark\squarkbar, \gluino\gluino, \squark\gluino, \squark\squark). The program allows to calculate total cross-sections as well as differential distributions in the transverse momentum p_t and the rapidity y of one of the outgoing particles. In addition cuts in p_t and y can easily be implemented.Comment: 12 pages, latex, no figures, Complete postscript file and FORTRAN source codes available from http://wwwcn.cern.ch/~mspira/prospino

AATF/Che-1-An RNA Binding Protein at the Nexus of DNA Damage Response and Ribosome Biogenesis

The DNA damage response (DDR) is a complex signaling network that is activated upon genotoxic stress. It determines cellular fate by either activating cell cycle arrest or initiating apoptosis and thereby ensures genomic stability. The Apoptosis Antagonizing Transcription Factor (AATF/Che-1), an RNA polymerase II-interacting transcription factor and known downstream target of major DDR kinases, affects DDR signaling by inhibiting p53-mediated transcription of pro-apoptotic genes and promoting cell cycle arrest through various pathways instead. Specifically, AATF was shown to inhibit p53 expression at the transcriptional level and repress its pro-apoptotic activity by direct binding to p53 protein and transactivation of anti-apoptotic genes. Solid and hematological tumors of various organs exploit this function by overexpressing AATF. Both copy number gains and high expression levels of AATF were associated with worse prognosis or relapse of malignant tumors. Recently, a number of studies have enabled insights into the molecular mechanisms by which AATF affects both DDR and proliferation. AATF was found to directly localize to sites of DNA damage upon laser ablation and interact with DNA repair proteins. In addition, depletion of AATF resulted in increased DNA damage and decrease of both proliferative activity and genotoxic tolerance. Interestingly, considering the role of ribosomal stress in the regulation of p53, more recent work established AATF as ribosomal RNA binding protein and enabled insights into its role as an important factor for rRNA processing and ribosome biogenesis. This Mini Review summarizes recent findings on AATF and its important role in the DDR, malignancy, and ribosome biogenesis

Squark production at the Tevatron

We have determined the QCD corrections to the production of squark-antisquark pairs in p anti p collisions at the Tevatron. If the next-to-leading order corrections are taken into account, the renormalization/factorization scale dependence of the theoretical prediction for the cross section is reduced considerably. The higher order corrections increase the production cross section at the Tevatron by about a factor two if we compare the next-to-leading order prediction at a scale near the sqaurk mass with the lowest order prediction for which, in the experimental analyses, the scale was identified with the invariant energy of the parton subprocess. This results in a rise of the experimental lower bound on the squark mass from the Tevatron by about 20 GeV. (orig.)Available from TIB Hannover: RA 2999(94-212) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Structural and Biochemical Studies of Actin in Complex with Synthetic Macrolide Tail Analogues

The actin filament-binding and filament-severing activities of the aplyronine, kabiramide, and reidispongiolide families of marine macrolides are located within the hydrophobic tail region of the molecule. Two synthetic tail analogues of aplyronine C (SF-01 and GC-04) are shown to bind to G-actin with dissociation constants of (285±33) and (132±13) nM, respectively. The crystal structures of actin complexes with GC-04, SF-01, and kabiramide C reveal a conserved mode of tail binding within the cleft that forms between subdomains (SD) 1 and 3. Our studies support the view that filament severing is brought about by specific binding of the tail region to the SD1/SD3 cleft on the upper protomer, which displaces loop-D from the lower protomer on the same half-filament. With previous studies showing that the GC-04 analogue can sever actin filaments, it is argued that the shorter complex lifetime of tail analogues with F-actin would make them more effective at severing filaments compared with plasma gelsolin. Structure-based analyses are used to suggest more reactive or targetable forms of GC-04 and SF-01, which may serve to boost the capacity of the serum actin scavenging system, to generate antibody conjugates against tumor cell antigens, and to decrease sputum viscosity in children with cystic fibrosis

SUSY-QCD decays of squarks and gluinos

The partial widths are determined for squark decays to gluinos and quarks, and gluino decays to squarks and quarks, respectively. The widths are calculated including one-loop SUSY-QCD corrections. The corrections amount to +30% to +50% for squark decays and -10% to +10% for gluino decays. We have derived the results in the DR and MS renormalization schemes, and we have demonstrated explicitly that the one-loop effective qqg and qqg couplings are equal in the limit of exact supersymmetry. (orig.)Available from TIB Hannover: RN 437(96-022) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Stop decays in SUSY-QCD

The partial widths are determined for stop decays to top quarks and gluinos, and gluino decays to stop particles and top quarks (depending on the masses of the particles involved). The widths are calculated including one-loop SUSY-QCD corrections. The radiative corrections for these strong-interaction decays are compared with the SUSY-QCD corrections for electroweak stop decays to quarks and neutralinos/charginos and top-quark decays to stops and neutralinos. (orig.)16 refs.Available from TIB Hannover: RA 2999(96-178) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Inactivation of Apoptosis Antagonizing Transcription Factor in tubular epithelial cells induces accumulation of DNA damage and nephronophthisis

Recent human genetic studies have suggested an intriguing link between ciliary signaling defects and altered DNA damage responses in nephronophthisis (NPH) and related ciliopathies. However, the molecular mechanism and the role of altered DNA damage response in kidney degeneration and fibrosis have remained elusive. We recently identified the kinase-regulated DNA damage response target Apoptosis Antagonizing Transcription Factor (AATF) as a master regulator of the p53 response. Here, we characterized the phenotype of mice with genetic deletion of Aatf in tubular epithelial cells. Mice were born without an overt phenotype, but gradually developed progressive kidney disease. Histology was notable for severe tubular atrophy and interstitial fibrosis as well as cysts at the corticomedullary junction, hallmarks of human nephronophthisis. Aatf deficiency caused ciliary defects as well as an accumulation of DNA double strand breaks. In addition to its role as a p53 effector, we found that AATF suppressed RNA: DNA hybrid (R loop) formation, a known cause of DNA double strand breaks, and enabled DNA double strand break repair in vitro. Genome-wide transcriptomic analysis of Aatf deficient tubular epithelial cells revealed several deregulated pathways that could contribute to the nephronophthisis phenotype, including alterations in the inflammatory response and anion transport. These results suggest that AATF is a regulator of primary cilia and a modulator of the DNA damage response, connecting two pathogenetic mechanisms in nephronophthisis and related ciliopathies

Squark and gluino production at hadron colliders

We have determined the theoretical predictions for the cross-sections of squark and gluino production at pp and pp colliders (Tevatron and LHC) in next-to-leading order of supersymmetric QCD. By reducing the dependence on the renormalization/factorization scale considerably, the theoretically predicted values for the cross-sections are much more stable if these higher-order corrections are implemented. If squarks and gluinos are discovered, this improved stability translates into a reduced error on the masses, as extracted experimentally from the size of the production cross-sections. The cross-sections increase significantly if the next-to-leading order corrections are included at a renormalization/factorization scale near the average mass of the produced massive particles. This rise results in improved lower bounds on squark and gluino masses. By contrast, the shape of the transverse-momentum and rapidity distributions remains nearly unchanged when the next-to-leading order corrections are included. (orig.)37 refs.Available from TIB Hannover: RA 2999(96-150) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

A protein-RNA interaction atlas of the ribosome biogenesis factor AATF

AATF is a central regulator of the cellular outcome upon p53 activation, a finding that has primarily been attributed to its function as a transcription factor. Recent data showed that AATF is essential for ribosome biogenesis and plays a role in rRNA maturation. AATF has been implicated to fulfil this role through direct interaction with rRNA and was identified in several RNA-interactome capture experiments. Here, we provide a first comprehensive analysis of the RNA bound by AATF using CLIP-sequencing. Interestingly, this approach shows predominant binding of the 45S pre-ribosomal RNA precursor molecules. Furthermore, AATF binds to mRNAs encoding for ribosome biogenesis factors as well as snoRNAs. These findings are complemented by an in-depth analysis of the protein interactome of AATF containing a large set of proteins known to play a role in rRNA maturation with an emphasis on the protein-RNA-complexes known to be required for the generation of the small ribosomal subunit (SSU). In line with this finding, the binding sites of AATF within the 45S rRNA precursor localize in close proximity to the SSU cleavage sites. Consequently, our multilayer analysis of the protein-RNA interactome of AATF reveals this protein to be an important hub for protein and RNA interactions involved in ribosome biogenesis

Gluino-pair production at the Tevatron

The next-to-leading order QCD corrections to the production of gluino pairs at the Tevatron are presented in this paper. Similar to the production of squark-antisquark pairs, the dependence of the cross section on the renormalization/factorization scale is reduced considerably by including the higher-order corrections. The cross section increases with respect to the lowest-order calculation which, in previous experimental analyses, had been evaluated at the scale of the invariant energy of the partonic subprocesses. (orig.)15 refs.Available from TIB Hannover: RA 2999(95-105) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman