Half a century of amyloids: past, present and future

Amyloid diseases are global epidemics with profound health, social and economic implications and yet remain without a cure. This dire situation calls for research into the origin and pathological manifestations of amyloidosis to stimulate continued development of new therapeutics. In basic science and engineering, the cross-ß architecture has been a constant thread underlying the structural characteristics of pathological and functional amyloids, and realizing that amyloid structures can be both pathological and functional in nature has fuelled innovations in artificial amyloids, whose use today ranges from water purification to 3D printing. At the conclusion of a half century since Eanes and Glenner's seminal study of amyloids in humans, this review commemorates the occasion by documenting the major milestones in amyloid research to date, from the perspectives of structural biology, biophysics, medicine, microbiology, engineering and nanotechnology. We also discuss new challenges and opportunities to drive this interdisciplinary field moving forward. This journal i

Motility and Chemotaxis in Tissue Penetration of Oral Epithelial Cell Layers by Treponema denticola

The ability to penetrate tissue is an important virulence factor for pathogenic spirochetes. Previous studies have recognized the role of motility in allowing pathogenic spirochetes to invade tissues and migrate to sites favorable for bacterial proliferation. However, the nature of the movements, whether they are random or controlled by chemotaxis systems, has yet to be established. In this study, we addressed the role of motility and chemotaxis in tissue penetration by the periodontal disease-associated oral spirochete Treponema denticola using an oral epithelial cell line-based experimental approach. Wild-type T. denticola ATCC 35405 was found to penetrate the tissue layers effectively, whereas a nonmotile mutant was unable to overcome the tissue barrier. Interestingly, the chemotaxis mutants also showed impaired tissue penetration. A cheA mutant that is motile but lacks the central kinase of the chemotaxis pathway showed only about 2 to 3% of the wild-type penetration rate. The two known chemoreceptors of T. denticola, DmcA and DmcB, also appear to be involved in the invasion process. The dmc mutants were actively motile but exhibited reduced tissue penetration of about 30 and 10% of the wild-type behavior, respectively. These data suggest that not only motility but also chemotaxis is involved in the tissue penetration by T. denticola

Association between single-nucleotide polymorphisms in DNA double-strand break repair genes and prostate cancer aggressiveness in the Spanish population.

BACKGROUND: Novel predictors of prognosis and treatment response for prostate cancer (PCa) are required to better individualize treatment. Single-nucleotide polymorphisms (SNPs) in four genes directly (XRCC5 (X-ray repair complementing defective repair in Chinese hamster cells 5) and XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6)) or indirectly (PARP1 and major vault protein (MVP)) involved in non-homologous end joining were examined in 494 Spanish PCa patients. METHODS: A total of 22 SNPs were genotyped in a Biotrove OpenArray NT Cycler. Clinical tumor stage, diagnostic PSA serum levels and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator. RESULTS: (XRCC6) rs2267437 appeared as a risk factor for developing more aggressive PCa tumors. Those patients carrying the GG genotype were at higher risk of developing bigger tumors (odds ratio (OR)=2.04, 95% confidence interval (CI) 1.26-3.29, P=0.004), present higher diagnostic PSA levels (OR=2.12, 95% CI 1.19-3.78, P=0.011), higher Gleason score (OR=1.65, 95% CI 1.01-2.68, P=0.044) and D'Amico higher risk tumors (OR=2.38, 95% CI 1.24-4.58, P=0.009) than those patients carrying the CC/CG genotypes. Those patients carrying the (MVP) rs3815824 TT genotype were at higher risk of presenting higher diagnostic PSA levels (OR=4.74, 95% CI 1.40-16.07, P=0.013) than those patients carrying the CC genotype. When both SNPs were analyzed in combination, those patients carrying the risk genotypes were at higher risk of developing D'Amico higher risk tumors (OR=3.33, 95% CI 1.56-7.17, P=0.002). CONCLUSIONS: We believe that for the first time, genetic variants at XRCC6 and MVP genes are associated with risk of more aggressive disease, and would be taken into account when assessing the malignancy of PCa.This work was subsidized by grants from the Instituto de Salud Carlos III (Ministerio de. Economía y Competitividad from Spain), ID: PI12/01867 and PI13/00412; and Instituto Canario de Investigación del Cáncer (ICIC-GR-F-14/11). Almudena Valenciano has a grant from the Instituto Canario de Investigación del Cáncer (ICIC)