Report to VicRoads: Extent of unlicensed driving - follow up Ref 143 - Alcohol Harms Inquiry

Unlicensed driving is a serious problem in many countries, despite ongoing improvements in traffic law enforcement practices and technology. The term "unlicensed driver" is generally used to refer to people who drive or ride a motor vehicle without a valid driver's licence, including those who: • Have let their licence expire, • Have been disqualified or suspended from driving, • Hold an inappropriate licence for the class of vehicle they drive, • Drive outside the restrictions of a special licence, • Don’t currently hold a licence, or • Have never held a licence (Watson, 2003, 2004a)...

Ac2PIM-responsive miR-150 and miR-143 Target Receptor-interacting Protein Kinase 2 and Transforming Growth Factor Beta-activated Kinase 1 to Suppress NOD2-induced Immunomodulators

Specific and coordinated regulation of innate immune receptor-driven signaling networks often determines the net outcome of the immune responses. Here, we investigated the cross-regulation of toll-like receptor (TLR)2 and nucleotide-binding oligomerization domain (NOD)2 pathways mediated by Ac2PIM, a tetra-acylated form of mycobacterial cell wall component and muramyl dipeptide (MDP), a peptidoglycan derivative respectively. While Ac2PIM treatment of macrophages compromised their ability to induce NOD2-dependent immunomodulators like cyclooxygenase (COX)-2, suppressor of cytokine signaling (SOCS)-3, and matrix metalloproteinase (MMP)-9, no change in the NOD2-responsive NO, TNF-alpha, VEGF-A, and IL-12 levels was observed. Further, genome-wide microRNA expression profiling identified Ac2PIM-responsive miR-150 and miR-143 to target NOD2 signaling adaptors, RIP2 and TAK1, respectively. Interestingly, Ac2PIM was found to activate the SRC-FAK-PYK2-CREB cascade via TLR2 to recruit CBP/P300 at the promoters of miR-150 and miR-143 and epigenetically induce their expression. Loss-of-function studies utilizing specific miRNA inhibitors establish that Ac2PIM, via the miRNAs, abrogate NOD2-induced PI3K-PKC delta-MAPK pathway to suppress beta-catenin-mediated expression of COX-2, SOCS-3, and MMP-9. Our investigation has thus underscored the negative regulatory role of Ac2PIM-TLR2 signaling on NOD2 pathway which could broaden our understanding on vaccine potential or adjuvant utilities of Ac2PIM and/or MDP.

Sapientia, 1982, Vol. XXXVII, nº 143 (número completo)

Contenido: La participación del ser I : hacia la verdadera noción de la participación / Octavio N. Derisi – La categorización metafísica del derecho según Santo Tomás / Carlos I. Massini – La ciencia como pensamiento crítico según Carlos R. Popper / William R. Darós – La restauración del tomismo en Fray José María Liqueno / Alberto Caturelli – La reducción de la metafísica clásica en Schelling / Juan Cruz Cruz – Notas y comentarios -- Bibliografía

80 C 143 U.S. Aeroplane carrier "Saratoga" in Guillard Cut- Panama Canal - Feb. 7, 1928

Leonard Carpenter Panama Canal Collection. Photographs: Views of Panama and the Canal. [Box 1] from the Special Collections & Area Studies Department, George A. Smathers Libraries, University of Florida.