Shotgun Cloning of Transposon Insertions in the Genome of Caenorhabditis elegans

We present a strategy to identify and map large numbers of transposon insertions in the genome of Caenorhabditis elegans. Our approach makes use of the mutator strain mut-7, which has germline-transposition activity of the Tc1/mariner family of transposons, a display protocol to detect new transposon insertions, and the availability of the genomic sequence of C. elegans. From a pilot insertional mutagenesis screen, we have obtained 351 new Tc1 transposons inserted in or near 219 predicted C. elegans genes. The strategy presented provides an approach to isolate insertions of natural transposable elements in many C. elegans genes and to create a large-scale collection of C. elegans mutants

Hook plate fixation of acute displaced lateral clavicle fractures: mid-term results and a brief literature overview

<p>Abstract</p> <p>Background</p> <p>The clavicle hook plate achieves like most other operative techniques, a high percentage of union and a low percentage of complications however concerns about long term complications still exist, particularly the involvement of the acromioclavicular joint.</p> <p>Methods</p> <p>To evaluate the results and long term effects in use of this plate we performed a retrospective analysis with a mean follow up of 65 months (5.4 years) of 28 consecutive patients with acute displaced lateral clavicle fractures, treated with the clavicle hook plate.</p> <p>Results</p> <p>Short term functional results in all patients were good to excellent. All but one patient had a united fracture (96%). Nine patients (32%) developed impingement symptoms and in 7 patients (25%) subacromial osteolysis was found. These findings resolved after plate removal. Twenty-four patients were re-evaluated at a mean follow-up period of 5.4 years. The Constant-Murley score was 97 and the DASH score was 3.5. Four patients (14%) developed acromioclavicular joint arthrosis of which one was symptomatic. Three patients (11%) had extra articular ossifications of which one was symptomatic. There was no relation between the impingement symptoms, subacromial osteolysis and development of acromioclavicular joint arthrosis or extra articular ossifications.</p> <p>Conclusions</p> <p>The clavicle hook plate is a good primary treatment option for the acute displaced lateral clavicle fracture with few complications. At mid term the results are excellent and no long term complications can be addressed to the use of the plate.</p

Hyperactivation of the G12-Mediated Signaling Pathway in Caenorhabditis elegans Induces a Developmental Growth Arrest via Protein Kinase C

AbstractThe G12 type of heterotrimeric G-proteins play an important role in development and behave as potent oncogenes in cultured cells [1–5]. However, little is known about the molecular nature of the components that act in the G12-signaling pathway in an organism. We characterized a C. elegans Gα subunit gene, gpa-12, which is a homolog of mammalian G12/G13α, and found that animals defective in gpa-12 are viable. Expression of activated GPA-12 (G12QL) results in a developmental growth arrest caused by a feeding behavior defect that is due to a dramatic reduction in pharyngeal pumping. To elucidate the molecular nature of the signaling pathways in which G12 participates, we screened for suppressors of the G12QL phenotype. We isolated 50 suppressors that contain mutations in tpa-1, which encodes two protein kinase C isoforms, TPA-1A and TPA-1B, most similar to PKCθ/δ. TPA-1 mediates the action of the tumor promoter PMA [6]. Expression of G12QL and treatment of wild-type animals with PMA induce an identical growth arrest caused by inhibition of larval feeding, which is dependent on TPA-1A and TPA-1B function. These results suggest that TPA-1 is a downstream target of both G12 signaling and PMA in modulating feeding and growth in C. elegans. Taken together, our findings provide a potential molecular mechanism for the transforming capability of G12 proteins

Effective spinless fermions in the strong coupling Kondo model

Starting from the two-orbital Kondo-lattice model with classical t_2g spins, an effective spinless fermion model is derived for strong Hund coupling J_H with a projection technique. The model is studied by Monte Carlo simulations and analytically using a uniform hopping approximation. The results for the spinless fermion model are in remarkable agreement with those of the original Kondo-lattice model, independent of the carrier concentration, and even for moderate Hund coupling J_H. Phase separation, the phase diagram in uniform hopping approximation, as well as spectral properties including the formation of a pseudo-gap are discussed for both the Kondo-lattice and the effective spinless fermion model in one and three dimensions.Comment: Revtex4, 10 pages, 15 figures, typos correcte

Invited Article: Direct phase mapping of broadband Laguerre-Gaussian metasurfaces

We report on the fabrication of metasurface phase plates consisting of gold nanoantenna arrays that generate Laguerre-Gaussian modes from a circularly polarized Gaussian input beam. The corresponding helical phase profiles with radial discontinuities are encoded in the metasurfaces by the orientation of the nanoantennas. A commonpath interferometer is used to determine the orbital angular momentum of the generated beams. Additionally, we employ digital holography to record the detailed phase profiles of the Laguerre-Gaussian modes. This method allows a simple and direct quantitative comparison of the measured phase profiles of the generated Laguerre-Gaussian beams with the theoretically expected phase profiles. Experiments with different laser sources demonstrate the broadband operation of the metasurface

Anticarbamylated protein antibodies are associated with long-term disability and increased disease activity in patients with early inflammatory arthritis:Results from the Norfolk Arthritis Register

Objectives: Anticarbamylated protein (anti-CarP) antibodies are a novel family of autoantibodies recently identified in patients with inflammatory arthritis. The aim of this study was to investigate their association with long-term outcomes of disability and disease activity over 20 years’ follow-up in a cohort of patients with inflammatory polyarthritis (IP).  Methods: Norfolk Arthritis Register recruited adults with recent-onset swelling of ≥2 joints for ≥4 weeks from 1990 to 2009. At baseline, Health Assessment Questionnaire (HAQ) and 28 joint disease activity scores (DAS28) were obtained, and C reactive protein, rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA) and anti-CarP antibodies were measured. Further HAQ scores and DAS28 were obtained at regular intervals over 20 years. Generalised estimating equations were used to test the association between anti-CarP antibody status and longitudinal HAQ and DAS28 scores; adjusting for age, gender, smoking status, year of inclusion and ACPA status. Analyses were repeated in subgroups stratified by ACPA status. The relative association of RF, ACPA and anti-CarP antibodies with HAQ and DAS28 scores was investigated using a random effects model.  Results: 1995 patients were included; 1310 (66%) were female. Anti-CarP antibodies were significantly associated with more disability and higher disease activity, HAQ multivariate β-coefficient (95% CI) 0.12 (0.02 to 0.21), and these associations remained significant in the ACPA-negative subgroups. The associations of RF, ACPA and anti-CarP antibodies were found to be additive in the random effects model.  Conclusions: Anti-CarP antibodies are associated with increased disability and higher disease activity in patients with IP. Our results suggest that measurement of anti-CarP antibodies may be useful in identifying ACPA-negative patients with worse long-term outcomes. Further, anti-CarP antibody status provided additional information about RF and ACPA

Left-right olfactory asymmetry results from antagonistic functions of voltage-activated calcium channels and the Raw repeat protein OLRN-1 in C. elegans

<p>Abstract</p> <p>Background</p> <p>The left and right AWC olfactory neurons in <it>Caenorhabditis elegans </it>differ in their functions and in their expression of chemosensory receptor genes; in each animal, one AWC randomly takes on one identity, designated AWC^OFF, and the contralateral AWC becomes AWC^ON. Signaling between AWC neurons induces left-right asymmetry through a gap junction network and a claudin-related protein, which inhibit a calcium-regulated MAP kinase pathway in the neuron that becomes AWC^ON.</p> <p>Results</p> <p>We show here that the asymmetry gene <it>olrn-1 </it>acts downstream of the gap junction and claudin genes to inhibit the calcium-MAP kinase pathway in AWC^ON. OLRN-1, a protein with potential membrane-association domains, is related to the <it>Drosophila </it>Raw protein, a negative regulator of JNK mitogen-activated protein (MAP) kinase signaling. <it>olrn-1 </it>opposes the action of two voltage-activated calcium channel homologs, <it>unc-2 </it>(CaV2) and <it>egl-19 </it>(CaV1), which act together to stimulate the calcium/calmodulin-dependent kinase CaMKII and the MAP kinase pathway. Calcium channel activity is essential in AWC^OFF, and the two AWC neurons coordinate left-right asymmetry using signals from the calcium channels and signals from <it>olrn-1</it>.</p> <p>Conclusion</p> <p><it>olrn-1 </it>and voltage-activated calcium channels are mediators and targets of AWC signaling that act at the transition between a multicellular signaling network and cell-autonomous execution of the decision. We suggest that the asymmetry decision in AWC results from the intercellular coupling of voltage-regulated channels, whose cross-regulation generates distinct calcium signals in the left and right AWC neurons. The interpretation of these signals by the kinase cascade initiates the sustained difference between the two cells.</p

X-ray Bright Active Galactic Nuclei in Massive Galaxy Clusters I: Number Counts and Spatial Distribution

We present an analysis of the X-ray bright point source population in 43 massive clusters of galaxies observed with the Chandra X-ray Observatory. We have constructed a catalog of 4210 rigorously selected X-ray point sources in these fields, which span a survey area of 4.2 square degrees. This catalog reveals a clear excess of sources when compared to deep blank-field surveys, which amounts to roughly 1 additional source per cluster, likely Active Galactic Nuclei (AGN) associated with the clusters. The excess sources are concentrated within the virial radii of the clusters, with the largest excess observed near the cluster centers. The average radial profile of the excess X-ray sources of the cluster are well described by a power law (N(r) ~ r^\beta) with an index of \beta ~ -0.5. An initial analysis using literature results on the mean profile of member galaxies in massive X-ray selected clusters indicates that the fraction of galaxies hosting X-ray AGN rises with increasing clustercentric radius, being approximately 5 to 10 times higher near the virial radius than in the central regions. This trend is qualitatively similar to that observed for star formation in cluster member galaxies.Comment: 18 Pages, 10 Figures, Submitted to MNRAS. Please contact Steven Ehlert ([email protected]) for higher resolution figures. Updated to reflect small changes requested by referee. This version has been accepted into MNRA