Induction of melanogenesis during the various melanoma growth phases and the role of tyrosinase, lysosome-associated membrane proteins, and p90 calnexin in the melanogenesis cascade

Melanin biosynthesis (melanogenesis) is a metabolic pathway exclusively expressed by melanocytes and melanoma cells, and is often altered and/or markedly elevated in the latter cells. The changes in melanogenesis may be responsible for some of the clinical and histopathological features unique to melanoma. Melanogenesis may also contribute to the malignant transformation of melanoma precursors (i.e., atypical moles [or dysplastic nevi]) to melanoma as seen in patients with the familial atypical multiple-mole-melanoma (FAMMM) syndrome. However, it does not appear to affect the multi-step growth phases of melanoma cells from radial to vertical and lastly metastatic growth phases. Within the melanosomal compartment, eu- and pheomelanin pigments are synthesized. Both tyrosinase and lysosome-associated membrane protein (LAMP) gene products play important roles in this process. A coordinated interaction between these two gene family products is required for melanogenesis to occur properly. p90 calnexin is a new melanosome-associated molecule that is presumed to function as a melanogenesis chaperone by controlling the assembly and folding of glycoprotein intermediates of tyrosinase and LAMP gene families.     

Spherulitic morphology of the matrix of thermoplastic PEEK/carbon fibre aromatic polymer composites

PEEK/carbon fibre composites (derived from APC-2) have been examined with a permanganic etching technique in order to reveal the crystalline, spherulitic morphology of the thermoplastic PEEK polymer matrix. The locations of the nucleation sites for spherulite growth have been categorized. Nucleation can occur both within the matrix and from the carbon fibres. Crystallization at lower temperatures favours matrix nucleation. Nucleation from fibres is dominated by sites associated with fibre-fibre contact. There is no evidence of “transcrystalline” growth. The study also identifies two types of crystal orientation effect in the polymer matrix. The first is a slight orientation that can occur in standard mouldings and is the result of the fibres constraining the shape of the volume into which spherulite growth can occur. The second effect produces abnormally high crystal orientation and is the result of improper processing at too low a melt temperature. Such conditions cause self-seeding during consolidation of laminates which, coupled with flow-induced orientation, can lead to directionally arranged spherulite precursors in different stages of morphological development.     

The establishment of the maximum permissible concentration of orlok in the air of a work area when used in agriculture

Inhaled Orlok causes changes in the CNS, blood morphology, renal function. The threshold concentration of Orlok is 0.17 mg/m3, its subthreshold concentration is 0.023 mg/m3, MAC in the workplace air is 0.05 mg/m3.     

Purification, characterization, and functional analysis of a truncated Klebsiella aerogenes UreE urease accessory protein lacking the histidine-rich carboxyl terminus

Klebsiella aerogenes UreE, one of four accessory proteins involved in urease metallocenter assembly, contains a histidine-rich C terminus (10 of the last 15 residues) that is likely to participate in metal ion coordination by this nickel-binding protein. To study the function of the histidine-rich region in urease activation, ureE in the urease gene cluster was mutated to result in synthesis of a truncated peptide, H144* UreE, lacking the final 15 residues. Urease activity in cells containing H144* UreE approached the activities for cells possessing the wild-type protein at nickel ion concentrations ranging from 0 to 1 mM in both nutrient-rich and minimal media. In contrast, clear reductions in urease activities were observed when two ureE deletion mutant strains were examined, especially at lower nickel ion concentrations. Surprisingly, the H144* UreE, like the wild-type protein, was readily purified with a nickel-nitrilotriacetic acid resin. Denaturing polyacrylamide gel electrophoretic analysis and N-terminal sequencing confirmed that the protein was a truncated UreE. Size exclusion chromatography indicated that the H144* UreE peptide associated into a homodimer, as known for the wild-type protein. The truncated protein was shown to cooperatively bind 1.9 +/- 0.2 Ni(II) ions as assessed by equilibrium dialysis measurements, compared with the 6.05 +/- 0.25 Ni ions per dimer reported previously for the native protein. These results demonstrate that the histidine-rich motif is not essential to UreE function and is not solely responsible for UreE nickel-binding ability. Rather, we propose that internal nickel binding sites of UreE participate in urease metallocenter assembly.