Phase-locking of a 2.7-THz quantum cascade laser to a mode-locked erbium-doped fibre laser

We demonstrate phase-locking of a 2.7-THz metalmetal waveguide quantum cascade laser (QCL) to an external microwave signal. The reference is the 15th harmonic, generated by a semiconductor superlattice nonlinear device, of a signal at 182 GHz, which itself is generated by a multiplier-chain (x2x3x2) from a microwave synthesizer at 15 GHz. Both laser and reference radiations are coupled into a hot electron bolometer mixer, resulting in a beat signal, which is fed into a phase-lock loop. Spectral analysis of the beat signal (see fig. 1) confirms that the QCL is phase locked. This result opens the possibility to extend heterodyne interferometers into the far-infrared range

Crop Updates 2002 - Pulse Research and Industry Development in Western Australia

This session covers seventy one papers from different authors: 1. 2001 PULSE INDUSTRY HIGHLIGHTS CONTRIBUTORS BACKGROUND 2001 REGIONAL ROUNDUP 2. Northern Agricultural Region, M. Harries, Department of Agriculture 3. Central Agricultural Region, R. French and I. Pritchard, Department of Agriculture 4. Great Southern and Lakes, N. Brandon, N. Runciman and S. White, Department of Agriculture 5. Esperance Mallee, M. Seymour, Department of Agriculture PULSE PRODUCTION AGRONOMY AND GENETIC IMPROVEMENT 6. Faba bean, P. White, Department of Agriculture 7. Germplasm evaluation, P. White, M. Seymour and M. Harries, Department of Agriculture 8. Variety evaluation, P. White, M. Harries, N. Brandon and M. Seymour, Department of Agriculture 9. Sowing rate and time of sowing, P. White, N. Brandon, M. Seymour and M. Harries, Department of Agriculture 10.Use of granular inoculum in the Great Southern, N. Brandon1, J. Howieson2 and R. Yates2 1Department of Agriculture, 2Centre for Rhizobium Studies, Murdoch University 11.Tolerance to post emergent herbicides, M. Seymour and M. Harries, Department of Agriculture 12.Herbicide tolerance of new varieties, H. Dhammu and T. Piper, Department of Agriculture Desi chickpea 13. Breeding highlights, T. Khan, Department of Agriculture 14. Variety evaluation, T. Khan and K. Regan, Department of Agriculture 15. Effect of genotype and environment on seed quality, N. Suizu1 and D. Diepeveen2 1School of Public Health, Curtin University of Technology 2Department of Agriculture 16. Seed discolouration, C. Veitch and P. White, Department of Agriculture 17. Foliar application on N increases seed yield and seed protein under terminal drought, J. Palta1,2, A. Nandwal3 and N. Turner1,2 , 1CSIRO Plant Industry, 2CLIMA, the University of Western Australia, 3Department of Botany, Haryana Agric University, Hisar, India 18. Tolerance to chilling at flowering, H. Clarke, CLIMA, The University of Western Australia 19. Molecular studies of ascochyta blight disease in chickpea, G. Dwyer1, H. Loo1, T. Khan2, K. Siddique3, M. Bellgard1 and M. Jones1 ,1WA State Agricultural Biotechnology Centre and Centre for Bioinformatics and Biological Computing, Murdoch University, 2Department of Agriculture, 3CLIMA, The University of Western Australia 20. Effect of row spacing and sowing rate on seed yield, G. Riethmuller and B. MacLeod, Department of Agriculture 21. Herbicide tolerance on marginal soil types, H. Dhammu and T. Piper, Department of Agriculture 22. Kabuli chickpea, K. Regan, Department of Agriculture 23. Variety and germplasm evaluation, T. Khan and K. Regan, Department of Agriculture 24. Premium quality kabuli chickpea development in the ORIA, K. Siddique1, K. Regan2, R. Shackles2 and P. Smith2 , 1 CLIMA, The University of Western Australia, 2Department of Agriculture 25. Evaluation of ascochylta resistant germplasm from Syria and Turkey, K. Siddique1, C. Francis1 and K. Regan2, 1CLIMA, University of Western Australia 2Department of Agriculture Field pea 26. Breeding highlights, T. Khan Department of Agriculture 27. Variety evaluation, T. Khan Department of Agriculture 28. Comparing the phosphorus requirement of field pea and wheat, M. Bolland and P. White, Department of Agriculture 29. Tolerance of field pea to post emergent herbicides, M. Seymour and N. Brandon, Department of Agriculture 30. Response of new varieties to herbicides, H. Dhammu and T. Piper, Department of Agriculture 31. Lentil, K. Regan, Department of Agriculture 32. Variety evaluation, K. Regan, N. Brandon, M. Harries and M. Seymour, Department of Agriculture 33. Interstate evaluation of advanced breeding lines developed in WA, K. Regan1, K. Siddique2 and M. Materne3, 1Department of Agriculture, 2CLIMA, University of Western Australia, 3Victorian Institute for Dryland Agriculture, Agriculture Victoria 34. Evaluation of germplasm from overseas and local projects, K. Regan1, J. Clements2, K.H.M. Siddique2 and C. Francis21Department of Agriculture, 2CLIMA, University of Western Australia 35. Evaluation of breeding lines developed in WA, K. Regan1, J. Clements2, K.H.M. Siddique2 and C. Francis21Department of Agriculture, 2CLIMA, University of Western Australia 36. Productivity and yield stability in Australia and Nepal, C. Hanbury, K. Siddique and C. Francis, CLIMA, the University of Western Australia Vetch 37. Germplasm evaluation, M. Seymour1, R. Matic2 and M. Tate3, 1Department of Agriculture, 2South Australian Research and Development Institute, 3University of Adelaide, Waite Campus 38. Tolerance of common vetch to post emergent herbicides, M. Seymour and N. Brandon, Department of Agriculture Narbon bean 39. Removing narbon bean from wheat, M. Seymour, Department of Agriculture 40. Tolerance to low rates of Roundup and Sprayseed, M. Seymour, Department of Agriculture 41. Lathyrus development, C. Hanbury, CLIMA, the University of Western Australia 42. Poultry feeding trials, C. Hanbury1 and B. Hughes2 ,1CLIMA, the University of Western Australia,2Pig and Poultry Production Institute, South Australia Pulse Species 43. Species time of sowing, B. French, Department of Agriculture 44. High value pulses in the Great Southern, N. Brandon and N. Runciman, Department of Agriculture 45. Time of Harvest for improved seed yields of pulses, G. Riethmuller and B. French, Department of Agriculture 46. Phosphate acquisition efficiency of pulse crops, P. Rees, Plant Biology, Faculty of Natural and Agricultural Sciences UWA DEMONSTRATION OF PULSES IN THE FARMING SYSTEM 47. Howzat desi chickpea in the northern region, M. Harries, Department of Agriculture 48. Field pea harvest losses in the Great Southern and Esperance region, N. Brandon and M. Seymour, Department of Agriculture 49. Timing of crop topping in field pea, N. Brandon and G. Riethmuller, Department of Agriculture DISEASE AND PEST MANAGEMENT 50. Ascochyta blight of chickpea, B. MacLeod, M. Harries and N. Brandon, Department of Agriculture 51. Evaluation of Australian management packages, 52. Screening foliar fungicides 53. Row spacing and row spraying 54. Ascochyta management package for 2002, B. MacLeod, Department of Agriculture 55. Epidemiology of aschochyta and botrytis disease of pulses, J. Galloway and B. MacLeod, Department of Agriculture 56. Ascochyta blight of chickpea 57. Black spot of field pea 58. Ascochyta blight of faba bean 59. Ascochyta blight of lentil 60. Botrytis grey mould of chickpea 61. Black spot spread: Disease models are based in reality, J. Galloway, Department of Agriculture 62. Black spot spread: Scaling-up field data to simulate ‘Bakers farm’, M. Salam, J. Galloway, A. Diggle and B. MacLeod, Department of Agriculture 63. Pulse disease diagnostics, N. Burges and D. Wright, Department of Agriculture Viruses in pulses 64. Incidence of virus diseases in chickpea, J. Hawkes1, D. Thackray1 and R. Jones1,2, 1CLIMA, The University of Western Australia 2Department of Agriculture Insect pests 65. Risk assessment of aphid feeding damage on pulses, O. Edwards, J. Ridsdill-Smith, and R. Horbury, CSIRO Entomology 66. Optimum spray timing to control aphid feeding damage of faba bean, F. Berlandier, Department of Agriculture 67. Incorporation of pea weevil resistance into a field pea variety, O. Byrne1 and D. Hardie2, 1CLIMA, The University of Western Australia, 2Department of Agriculture 68. Screening wild chickpea species for resistance to Helicoverpa, T. Ridsdill-Smith1 and H. Sharma2,1CSIRO, Entomology, 2ICRISAT, Hyderabad 69. Field strategies to manage the evolution of pea weevil resistance in transgenic field pea, M. de Sousa Majer1, R. Roush2, D. Hardie3, R. Morton4 and T. Higgins4, 1Curtin University of Technology, 2Waite Campus, University of Adelaide, 3Department of Agriculture, 4CSIRO Plant Industry, Canberra 70. ACKNOWLEDGMENTS 71. Appendix 1: Summary of previous result

Extensive Crosstalk between O-GlcNAcylation and Phosphorylation Regulates Akt Signaling

O-linked N-acetylglucosamine glycosylations (O-GlcNAc) and O-linked phosphorylations (O-phosphate), as two important types of post-translational modifications, often occur on the same protein and bear a reciprocal relationship. In addition to the well documented phosphorylations that control Akt activity, Akt also undergoes O-GlcNAcylation, but the interplay between these two modifications and the biological significance remain unclear, largely due to the technique challenges. Here, we applied a two-step analytic approach composed of the O-GlcNAc immunoenrichment and subsequent O-phosphate immunodetection. Such an easy method enabled us to visualize endogenous glycosylated and phosphorylated Akt subpopulations in parallel and observed the inhibitory effect of Akt O-GlcNAcylations on its phosphorylation. Further studies utilizing mass spectrometry and mutagenesis approaches showed that O-GlcNAcylations at Thr 305 and Thr 312 inhibited Akt phosphorylation at Thr 308 via disrupting the interaction between Akt and PDK1. The impaired Akt activation in turn resulted in the compromised biological functions of Akt, as evidenced by suppressed cell proliferation and migration capabilities. Together, this study revealed an extensive crosstalk between O-GlcNAcylations and phosphorylations of Akt and demonstrated O-GlcNAcylation as a new regulatory modification for Akt signaling

Coexpression Network Analysis in Abdominal and Gluteal Adipose Tissue Reveals Regulatory Genetic Loci for Metabolic Syndrome and Related Phenotypes

Metabolic Syndrome (MetS) is highly prevalent and has considerable public health impact, but its underlying genetic factors remain elusive. To identify gene networks involved in MetS, we conducted whole-genome expression and genotype profiling on abdominal (ABD) and gluteal (GLU) adipose tissue, and whole blood (WB), from 29 MetS cases and 44 controls. Co-expression network analysis for each tissue independently identified nine, six, and zero MetS–associated modules of coexpressed genes in ABD, GLU, and WB, respectively. Of 8,992 probesets expressed in ABD or GLU, 685 (7.6%) were expressed in ABD and 51 (0.6%) in GLU only. Differential eigengene network analysis of 8,256 shared probesets detected 22 shared modules with high preservation across adipose depots (DABD-GLU = 0.89), seven of which were associated with MetS (FDR P<0.01). The strongest associated module, significantly enriched for immune response–related processes, contained 94/620 (15%) genes with inter-depot differences. In an independent cohort of 145/141 twins with ABD and WB longitudinal expression data, median variability in ABD due to familiality was greater for MetS–associated versus un-associated modules (ABD: 0.48 versus 0.18, P = 0.08; GLU: 0.54 versus 0.20, P = 7.8×10−4). Cis-eQTL analysis of probesets associated with MetS (FDR P<0.01) and/or inter-depot differences (FDR P<0.01) provided evidence for 32 eQTLs. Corresponding eSNPs were tested for association with MetS–related phenotypes in two GWAS of >100,000 individuals; rs10282458, affecting expression of RARRES2 (encoding chemerin), was associated with body mass index (BMI) (P = 6.0×10−4); and rs2395185, affecting inter-depot differences of HLA-DRB1 expression, was associated with high-density lipoprotein (P = 8.7×10−4) and BMI–adjusted waist-to-hip ratio (P = 2.4×10−4). Since many genes and their interactions influence complex traits such as MetS, integrated analysis of genotypes and coexpression networks across multiple tissues relevant to clinical traits is an efficient strategy to identify novel associations

Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer

A common key regulator of oncogenic signaling pathways in multiple tumor types is the unique isomerase Pin1. However, available Pin1 inhibitors lack the required specificity and potency. Using mechanism-based screening, here we find that all-trans retinoic acid (ATRA)--a therapy for acute promyelocytic leukemia (APL) that is considered the first example of targeted therapy in cancer, but its drug target remains elusive--inhibits and degrades active Pin1 selectively in cancer cells by directly binding to the substrate phosphate- and proline-binding pockets in the Pin1 active site. ATRA-induced Pin1 ablation degrades the fusion oncogene PML-RARα and treats APL in cell and animal models and human patients. ATRA-induced Pin1 ablation also inhibits triple negative breast cancer cell growth in human cells and in animal models by acting on many Pin1 substrate oncogenes and tumor suppressors. Thus, ATRA simultaneously blocks multiple Pin1-regulated cancer-driving pathways, an attractive property for treating aggressive and drug-resistant tumors

Protooncogene TCL1b functions as an Akt kinase co-activator that exhibits oncogenic potency in vivo

Protooncogene T-cell leukemia 1 (TCL1), which is implicated in human T-cell prolymphocytic leukemia (T-PLL), interacts with Akt and enhances its kinase activity, functioning as an Akt kinase co-activator. Two major isoforms of TCL1 Protooncogenes (TCL1 and TCL1b) are present adjacent to each other on human chromosome 14q.32. In human T-PLL, both TCL1 and TCL1b are activated by chromosomal translocation. Moreover, TCL1b-transgenic mice have never been created. Therefore, it remains unclear whether TCL1b itself, independent of TCL1, exhibits oncogenicity. In co-immunoprecipitation assays, both ectopic and endogenous TCL1b interacted with Akt. In in vitro Akt kinase assays, TCL1b enhanced Akt kinase activity in dose- and time-dependent manners. Bioinformatics approaches utilizing multiregression analysis, cluster analysis, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway mapping, Venn diagrams and Gene Ontology (GO) demonstrated that TCL1b showed highly homologous gene-induction signatures similar to Myr-Akt or TCL1. TCL1b exhibited oncogenicity in in vitro colony-transformation assay. Further, two independent lines of b-actin promoter-driven TCL1b-transgenic mice developed angiosarcoma on the intestinal tract. Angiosarcoma is a rare form of cancer in humans with poor prognosis. Using immunohistochemistry, 11 out of 13 human angiosarcoma samples were positively stained with both anti-TCL1b and anti-phospho-Akt antibodies. Consistently, in various cancer tissues, 69 out of 146 samples were positively stained with anti-TCL1b, out of which 46 were positively stained with antiphospho- Akt antibodies. Moreover, TCL1b structure-based inhibitor ‘TCL1b-Akt-in’ inhibited Akt kinase activity in in vitro kinase assays and PDGF (platelet-derived growth factor)-induced Akt kinase activities—in turn, ‘TCL1b-Akt-in’ inhibited cellular proliferation of sarcoma. The current study disclosed TCL1b bears oncogenicity and hence serves as a novel therapeutic target for human neoplastic diseases

Regulation of NF-κB Signaling by Pin1-Dependent Prolyl Isomerization and Ubiquitin-Mediated Proteolysis of p65/RelA

10.1016/S1097-2765(03)00490-8Molecular Cell1261413-1426MOCE

Identification of RNA aptamer which specifically interacts with PtdIns(3)P

The phosphinositide Ptdlns(3)P plays an important role in autophagy; however, the detailed mechanism of its activity remains unclear. Here, we used a Systematic Evolution of Ligands by EXponential enrichment (SELEX) screening approach to identify an RNA aptamer of 40 nucleotides that specifically recognizes and binds to intracellular lysosomal Ptdlns(3)P. Binding occurs in a magnesium concentration- and pH-dependent manner, and consequently inhibits autophagy as determined by LC3II/I conversion, p62 degradation, formation of LC3 puncta, and lysosomal accumulation of Phafin2. These effects in turn inhibited lysosomal acidification, and the subsequent hydrolytic activity of cathepsin D following induction of autophagy. Given the essential role of Ptdlns(3)P as a key targeting molecule for autophagy induction, identification of this novel Ptdlns(3)P RNA aptamer provides new opportunities for investigating the biological functions and mechanisms of phosphoinositides. (C) 2019 The Authors. Published by Elsevier Inc