A Mutation in Amino Acid Permease AAP6 Reduces the Amino Acid Content of the Arabidopsis Sieve Elements but Leaves Aphid Herbivores Unaffected.

The aim of this study was to investigate the role of the amino acid permease gene AAP6 in regulating phloem amino acid composition and then to determine the effects of this altered diet on aphid performance. A genotype of Arabidopsis thaliana (L.) was produced in which the function of the amino acid permease gene AAP6 (At5g49630) was abolished. Plants homozygous for the insertionally inactivated AAP6 gene had a significantly larger mean rosette width than the wild type and a greater number of cauline leaves. Seeds from the aap6 mutant were also significantly larger than those from the wild-type plants. Sieve element (SE) sap was collected by aphid stylectomy and the amino acids derivatized, separated, and quantified using Capillary Electrophoresis with Laser Induced Fluorescence (CE-LIF). In spite of the large variation across samples, the total amino acid concentration of SE sap of the aap6 mutant plants was significantly lower than that of the wild-type plants. The concentrations of lysine, phenylalanine, leucine, and aspartic acid were all significantly lower in concentration in the aap6 mutant plants compared with wild-type plants. This is the first direct demonstration of a physiological role for an amino acid transporter in regulating SE composition in vivo. The amino acid availability in sieve element sap is thought to be the major limiting factor for aphid growth and reproduction. Despite the changes in their diet, the aphid Myzus persicae(Sulzer) displayed only small changes in feeding behaviour on mutant plants when measured using the Electronic Penetration Graph (EPG) technique. Salivation by the aphid into the SE (E1 phase) was increased on mutant plants but there was no significant effect on other feeding EPG behaviours, or in the rate of honeydew production. Consistent with the small effect on aphid feeding behaviour, there was only a small effect of reduced sieve element amino acid concentration on aphid reproduction. The data are discussed in relation to the regulation of phloem composition and the role of phloem amino acids in regulating aphid performance

Hadron Spectrum with Wilson fermions

We present results of a high statistics study of the quenched spectrum using Wilson fermions at $\beta=6.0$ on $32^3 \times 64$ lattices. We calculate the masses of mesons and baryons composed of both degenerate and non-degenerate quarks. Using non-degenerate quark combinations allows us to study baryon mass splittings in detail. We find significant deviations from the lowest order chiral expansion, deviations that are consistent with the expectations of quenched chiral perturbation theory. We find that there is a $\sim 20$ systematic error in the extracted value of $m_s$, depending on the meson mass ratio used to set its value. Using the largest estimate of $m_s$ we find that the extrapolated octet mass-splittings are in agreement with the experimental values, as is $M_\Delta - M_N$, while the decuplet splittings are 30% smaller than experiment. Combining our results with data from the GF11 collaboration we find considerable ambiguity in the extrapolation to the continuum limit. Our preferred values are $M_N / M_\rho = 1.38(7)$ and $M_\Delta / M_\rho = 1.73(10)$, suggesting that the quenched approximation is good to only $\sim 10-15$. We also analyze the $O(ma)$ discretization errors in heavy quark masses.Comment: 52 pages. Tex. Modified "axis" source for figures also included. Needs macro packages lanlmac and epsf. Uses hyperbasics if available. Significant number of typographical errors correcte

Universal Scaling of the Chiral Condensate in Finite-Volume Gauge Theories

We confront exact analytical predictions for the finite-volume scaling of the chiral condensate with data from quenched lattice gauge theory simulations. Using staggered fermions in both the fundamental and adjoint representations, and gauge groups SU(2) and SU(3), we are able to test simultaneously all of the three chiral universality classes. With overlap fermions we also test the predictions for gauge field sectors of non-zero topological charge. Excellent agreement is found in most cases, and the deviations are understood in the others.Comment: Expanded discussion of overlap fermion results. 17 pages revtex, 7 postscript figure

Quenched chiral logarithms in lattice QCD with exact chiral symmetry

We examine quenched chiral logarithms in lattice QCD with overlap Dirac quark. For 100 gauge configurations generated with the Wilson gauge action at $\beta = 5.8$ on the $8^3 \times 24$ lattice, we compute quenched quark propagators for 12 bare quark masses. The pion decay constant is extracted from the pion propagator, and from which the lattice spacing is determined to be 0.147 fm. The presence of quenched chiral logarithm in the pion mass is confirmed, and its coefficient is determined to be $\delta = 0.203 \pm 0.014$, in agreement with the theoretical estimate in quenched chiral perturbation theory. Further, we obtain the topological susceptibility of these 100 gauge configurations by measuring the index of the overlap Dirac operator. Using a formula due to exact chiral symmetry, we obtain the $\eta'$ mass in quenched chiral perturbation theory, $m_{\eta'} = (901 \pm 64)$ Mev, and an estimate of $\delta = 0.197 \pm 0.027$, which is in good agreement with that determined from the pion mass.Comment: 24 pages, 6 EPS figures; v2: some clarifications added, to appear in Physical Review

Low-lying fermion modes, topology and light hadrons in quenched QCD

We explore the properties of low lying eigenmodes of fermions in the quenched approximation of lattice QCD. The fermion action is a recently proposed overlap action and has exact chiral symmetry. We find that chiral zero-eigenvalue modes are localized in space and their positions correlate strongly with the locations (as defined through the density of pure gauge observables) of instantons of the appropriate charge. Nonchiral modes are also localized with peaks which are strongly correlated with the positions of both charges of instantons. These correlations slowly die away as the fermion eigenvalue rises. Correlators made of quark propagators restricted to these modes closely reproduce ordinary hadron correlators at small quark mass in many channels. Our results are in qualitative agreement with the expectations of instanton liquid models.Comment: 21 pages, Revtex, 21 postscript figures. COLO-HEP-45

Failure to obtain adequate anaesthesia associated with a bifid mandibular canal: a case report

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.The inferior alveolar nerve (IAN) block is the most common method for obtaining mandibular anaesthesia in dental practice but it is estimated to have a success rate of only 80 to 85 per cent. Causes of failure include problems with operator technique and anatomical variation between individuals. This case report involves a patient who received IAN blocks on two separate occasions that resulted in only partial anaesthesia of the ipsilateral side of the mandible. Radiographic assessment disclosed the presence of bifid mandibular canals that were present bilaterally and that may have affected the outcomes of the local anaesthetic procedures. Previous studies of bifid mandibular canals are reviewed and suggestions provided that should enable clinicians to differentially diagnose, and then manage, cases where IAN blocks result in inadequate mandibular anaesthesia.K Lew, G Townsen

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology

Papillary carcinoma of the thyroid: methylation is not involved in the regulation of MET expression

Hypomethylation has been reported to be responsible for the activation of several oncogenes. The possibility that hypomethylation is involved in the regulation of MET transcription was investigated through the analysis of the methylation status of one CpG island containing 43 CpGs in six cases of papillary carcinoma, in the corresponding normal thyroid tissue, and in two cases of hyperplastic goitre. Evidence of methylation was not found in any of the analysed CpG. © 2004 Cancer Research UK

B Cells Participate in Thymic Negative Selection of Murine Auto-reactive CD4+ T Cells

It is well documented that thymic epithelial cells participate in the process of negative selection in the thymus. In recent years it was reported that also dendritic cells enter the thymus and contribute to this process, thus allowing for the depletion of thymocytes that are specific to peripherally expressed self-antigens. Here we report that also B cells may take part in the elimination of auto-reactive thymocytes. Using a unique mouse model we show that B cells induce negative selection of self-reactive thymocytes in a process that leads to the deletion of these cells whereas regulatory T cells are spared. These findings have direct implication in autoimmunity, as expression of a myelin antigen by B cells in the thymus renders the mice resistant to autoimmune inflammation of the CNS