Mechanical Translation

Contains research objectives and reports on three research projects.National Science Foundation (Grant G-16843)National Science Foundation (Grant G-13903

Depletion of TDP-43 affects Drosophila motoneurons terminal synapsis and locomotive behavior

Pathological modifications in the highly conserved and ubiquitously expressed heterogeneous ribonucleoprotein TDP-43 were recently associated to neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), a late-onset disorder that affects predominantly motoneurons [Neumann, M. et al. (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130-133, Sreedharan, J. et al. (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319, 1668-1672, Kabashi, E. et al. (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat. Genet. 40, 572-574]. However, the function of TDP-43 in vivo is unknown and a possible direct role in neurodegeneration remains speculative. Here, we report that flies lacking Drosophila TDP-43 appeared externally normal but presented deficient locomotive behaviors, reduced life span and anatomical defects at the neuromuscular junctions. These phenotypes were rescued by expression of the human protein in a restricted group of neurons including motoneurons. Our results demonstrate the role of this protein in vivo and suggest an alternative explanation to ALS pathogenesis that may be more due to the lack of TDP 43 function than to the toxicity of the aggregates. © 2009 Federation of European Biochemical Societies

TDP-43 regulates drosophila neuromuscular junctions growth by modulating futsch/MAP1B levels and synaptic microtubules organization

TDP-43 is an evolutionarily conserved RNA binding protein recently associated with the pathogenesis of different neurological diseases. At the moment, neither its physiological role in vivo nor the mechanisms that may lead to neurodegeneration are well known. Previously, we have shown that TDP-43 mutant flies presented locomotive alterations and structural defects at the neuromuscular junctions. We have now investigated the functional mechanism leading to these phenotypes by screening several factors known to be important for synaptic growth or bouton formation. As a result we found that alterations in the organization of synaptic microtubules correlate with reduced protein levels in the microtubule associated protein futsch/MAP1B. Moreover, we observed that TDP-43 physically interacts with futsch mRNA and that its RNA binding capacity is required to prevent futsch down regulation and synaptic defects. © 2011 Godena et al

The acquisition of Sign Language: The impact of phonetic complexity on phonology

Research into the effect of phonetic complexity on phonological acquisition has a long history in spoken languages. This paper considers the effect of phonetics on phonological development in a signed language. We report on an experiment in which nonword-repetition methodology was adapted so as to examine in a systematic way how phonetic complexity in two phonological parameters of signed languages — handshape and movement — affects the perception and articulation of signs. Ninety-one Deaf children aged 3–11 acquiring British Sign Language (BSL) and 46 hearing nonsigners aged 6–11 repeated a set of 40 nonsense signs. For Deaf children, repetition accuracy improved with age, correlated with wider BSL abilities, and was lowest for signs that were phonetically complex. Repetition accuracy was correlated with fine motor skills for the youngest children. Despite their lower repetition accuracy, the hearing group were similarly affected by phonetic complexity, suggesting that common visual and motoric factors are at play when processing linguistic information in the visuo-gestural modality

Probing BFKL Dynamics in the Dijet Cross Section at Large Rapidity Intervals in ppbar Collisions at sqrt{s}=1800 and 630 GeV

Inclusive dijet production at large pseudorapidity intervals (delta_eta) between the two jets has been suggested as a regime for observing BFKL dynamics. We have measured the dijet cross section for large delta_eta in ppbar collisions at sqrt{s}=1800 and 630 GeV using the DO detector. The partonic cross section increases strongly with the size of delta_eta. The observed growth is even stronger than expected on the basis of BFKL resummation in the leading logarithmic approximation. The growth of the partonic cross section can be accommodated with an effective BFKL intercept of a_{BFKL}(20GeV)=1.65+/-0.07.Comment: Published in Physical Review Letter

Search for Electroweak Production of Single Top Quarks in ppbar Collisions

We present a search for electroweak production of single top quarks in the electron+jets and muon+jets decay channels. The measurements use ~90 pb^-1 of data from Run 1 of the Fermilab Tevatron collider, collected at 1.8 TeV with the DZero detector between 1992 and 1995. We use events that include a tagging muon, implying the presence of a b jet, to set an upper limit at the 95% confidence level on the cross section for the s-channel process ppbar->tb+X of 39 pb. The upper limit for the t-channel process ppbar->tqb+X is 58 pb.Comment: 11 pages, 2 figures. This is the published versio

A Quasi-Model-Independent Search for New Physics at Large Transverse Momentum

We apply a quasi-model-independent strategy ("Sleuth") to search for new high p_T physics in approximately 100 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV collected by the DZero experiment during 1992-1996 at the Fermilab Tevatron. Over thirty-two e mu X, W+jets-like, Z+jets-like, and 3(lepton/photon)X exclusive final states are systematically analyzed for hints of physics beyond the standard model. Simultaneous sensitivity to a variety of models predicting new phenomena at the electroweak scale is demonstrated by testing the method on a particular signature in each set of final states. No evidence of new high p_T physics is observed in the course of this search, and we find that 89% of an ensemble of hypothetical similar experimental runs would have produced a final state with a candidate signal more interesting than the most interesting observed in these data.Comment: 28 pages, 17 figures. Submitted to Physical Review

Search for R-parity Violating Supersymmetry in Dimuon and Four-Jets Channel

We present results of a search for R-parity-violating decay of the neutralino chi_1^0, taken to be the Lightest Supersymmetric Particle. It is assumed that this decay proceeds through one of the lepton-number violating couplings lambda-prime_2jk (j=1,2; k=1,2,3). This search is based on 77.5 pb-1 of data, collected by the D0 experiment at the Fermilab Tevatron in ppbar collisions at a center of mass energy of 1.8 TeV in 1992-1995.Comment: 10 pages, 3 figure

Search for bottom squarks in pbarp collisions at sqrt(s)=1.8 TeV

We report on a search for bottom squarks produced in pbarp collisions at sqrt(s) = 1.8 TeV using the D0 detector at Fermilab. Bottom squarks are assumed to be produced in pairs and to decay to the lightest supersymmetric particle (LSP) and a b quark with branching fraction of 100%. The LSP is assumed to be the lightest neutralino and stable. We set limits on the production cross section as a function of bottom squark mass and LSP mass.Comment: 5 pages, Latex. submitted 3-12-1999 to PRD - Rapid Communicatio

Search for New Physics Using Quaero: A General Interface to D0 Event Data

We describe Quaero, a method that i) enables the automatic optimization of searches for physics beyond the standard model, and ii) provides a mechanism for making high energy collider data generally available. We apply Quaero to searches for standard model WW, ZZ, and ttbar production, and to searches for these objects produced through a new heavy resonance. Through this interface, we make three data sets collected by the D0 experiment at sqrt(s)=1.8 TeV publicly available.Comment: 7 pages, submitted to Physical Review Letter