c-Jun N-Terminal Kinase 1 Is Required for Toll-Like Receptor 1 Gene Expression in Macrophages

P. 5027-5034The regulation of innate immune responses to pathogens occurs through the interaction of Toll-like receptors (TLRs) with pathogen-associated molecular patterns and the activation of several signaling pathways whose contribution to the overall innate immune response to pathogens is poorly understood. We demonstrate a mechanism of control of murine macrophage responses mediated by TLR1/2 heterodimers through c-Jun N-terminal kinase 1 (JNK1) activity. JNK controls tumor necrosis factor alpha production and TLR-mediated macrophage responses to Borrelia burgdorferi, the causative agent of Lyme disease, and the TLR1/TLR2-specific agonist PAM3CSK4. JNK1, but not JNK2, activity regulates the expression of the tlr1 gene in the macrophage cell line RAW264.7, as well as in primary CD11b cells. We also show that the proximal promoter region of the human tlr1 gene contains an AP-1 binding site that is subjected to regulation by the kinase and binds two complexes that involve the JNK substrates c-Jun, JunD, and ATF-2. These results demonstrate that JNK1 regulates the response to TLR1/2 ligands and suggest a positive feedback loop that may serve to increase the innate immune response to the spirocheteS

Fatigue Precracking Time Estimates for Three-Point Bending Specimens

Specimens containing sharp cracks are needed in certain types of mechanical tests, first and foremost for fracture toughness measurement of materials. Their use, however, is not just limited to this type of test. Another category of experiments deals with characterizing nonlinear vibrations of beams containing breathing cracks. To produce cracked beam specimens, fatigue cracks can be grown ahead of sharp notches under controlled loading. ASTM E399 and ASTM E1820 standards provide guidance on such procedures for preparation of fracture toughness test specimens. However, certain issues which might become important in testing of vibrations of cracked beams, such as the time required for specimen preparation is not addressed in these standards. In this article, both low cycle fatigue methods and linear elastic fracture mechanics methods are used to estimate the number of loading cycles required to have a crack of desired length at the notch tip. Calculation results are compared with experimental ones, and the effects of various factors influencing the required number of loading cycles for a certain crack size are discussed

MESOPOROUS SULPHATE DOPED HYDROXYAPATITE NANOPARTICLES FOR CONTROLLED RELEASE OF PROTEINS

The purpose of this study is to synthesize and characterize the mesoporous nanostructure of Hydroxyapatite (HA), evaluate the impact of the addition of sulphate ions (SO₄2-) on the microstructure properties of HA, and assess the ability of the prepared materials to be used as a carrier for Bovine serum albumin (BSA) protein. This study successfully synthesized 0.07 mole of SO₄2- substituted HA using the reflux microwave-assisted wet precipitation method and fully characterized it using modern techniques. In particular, XRD, XPS, Raman, FESEM, and BET techniques were used to explore the microstructure properties of materials. The results shows that the addition of SO₄2- ions revealed increasing the lattice parameters and surface area of HA, and the particles shape was changed from semi-spherical to rod like shape. Adsorption and desorption of protein molecules were evaluated using BSA protein for 24h at 37°C. BSA loading capacity and release behaviours were significantly improved with the incorporation of SO₄2- ions. The SO₄-HA materials hold a promising future for being used as a carrier for protein molecules

MESOPOROUS SULPHATE DOPED HYDROXYAPATITE NANOPARTICLES FOR CONTROLLED RELEASE OF PROTEINS

The purpose of this study is to synthesize and characterize the mesoporous nanostructure of Hydroxyapatite (HA), evaluate the impact of the addition of sulphate ions (SO42-) on the microstructure properties of HA, and assess the ability of the prepared materials to be used as a carrier for Bovine serum albumin (BSA) protein. This study successfully synthesized 0.07 mole of SO42- substituted HA using the reflux microwave-assisted wet precipitation method and fully characterized it using modern techniques. In particular, XRD, XPS, Raman, FESEM, and BET techniques were used to explore the micro-structure properties of materials. The results shows that the addition of SO42- ions amplified the lattice parameters and surface area of HA, and the particles shape was changed from semi-spherical to rod like shape. Adsorption and desorption of protein molecules were evaluated using BSA protein for 24 h at 37°C. BSA loading capacity and release behaviours were significantly improved with the incorporation of SO42- ions. The SO4- HA materials hold a promising future for being used as a carrier for protein molecules