A heterologously expressed form of the human Parkinson diseaseassociated protein α-synuclein with a 10-residue N-terminal extension is shown to form a stable tetramer in the absence of lipid bilayers or micelles. Sequential NMR assignments, intramonomer nuclear Overhauser effects, and circular dichroism spectra are consistent with transient formation of α-helices in the first 100 Nterminal residues of the 140-residue α-synuclein sequence. Total phosphorus analysis indicates that phospholipids are not associated with the tetramer as isolated, and chemical cross-linking experiments confirm that the tetramer is the highest-order oligomer present at NMR sample concentrations. Image reconstruction from electron micrographs indicates that a symmetric oligomer is present, with three-or fourfold symmetry. Thermal unfolding experiments indicate that a hydrophobic core is present in the tetramer. A dynamic model for the tetramer structure is proposed, based on expected close association of the amphipathic central helices observed in the previously described micelle-associated "hairpin" structure of α-synuclein. T he protein α-synuclein (αSyn) is associated with the two most prevalent neurodegenerative diseases, Parkinson disease (PD) and Alzheimer's disease (AD). The presence of αSyn-rich aggregates (Lewy bodies) in neurons of the substantia nigra is the defining histopathological hallmark of PD, and is used to differentiate PD from other neurological disorders (1). Monogenic point mutations (A30P, A53T, and E46K) as well as gene duplication and triplication of the αSyn locus have been identified as causal factors of early onset familial PD; E46K has also been associated with Lewy body dementia, the second most common form of dementia after AD (2-4).αSyn is small (140 residues), and though the C-terminal region (∼residues 100-140) is highly acidic and expected to be disordered, the first 100 residues are predicted to be structured and to have α-helical propensity (SI Appendix, Fig. S1). Stable helical structures have been detected by circular dichroism (CD) and NMR when αSyn is incubated with detergent micelles and lipid vesicles (5, 6). Soluble αSyn is typically referred to as an "intrinsically disordered" protein (7,8). However, we herein report the biophysical characterization of a purified soluble form of αSyn that is oligomeric and fractionally occupies helical structures in the absence of micelles or vesicles. The αSyn construct used in our work is purified by use of an N-terminal GST affinity tag under mild conditions to preserve any native structure. After removal of the GST tag, a 10-residue N-terminal extension remains on the αSyn. However, the similarity of the 1 H, 15 N heteronuclear single-quantum coherence (HSQC) fingerprint of our αSyn construct (SI Appendix, Figs. S2 and S3) to those reported by other groups for αSyn suggests that the N-terminal extension does not change structural tendencies significantly. The αSyn construct described here is not toxic to membranes or cells, does not readily aggregate or ...
Candida species are yeasts and within the oral cavity, Candida albicans is the most frequently isolated. There is clear evidence that C. albicans adheres to oral surfaces including acrylic dentures and mucosa. The mechanisms of attachment differ, with candidal adhesion to inert surfaces under the control of hydrophobic and electrostatic forces and adhesion to mucosa dependent on a number of complex ligand-recognition systems. Other factors within the oral environment such as saliva, pH, bacteria and hyphal formation have been shown to influence adhesion of candida species to surfaces in the mouth.
Certaih systemic cenditions and/or defects in tlile irmmume sy,stem may JDt:edisJ!)Qse tliie host to oral candielal infecti0n and tliie commenest ferm of oral 1 cam~ielosis is candida-associatecl tilernture stomatitis.IJntil recently tliier-e has been cemtrev.ersy coneerrniAg 1 t!;le aeti010!iJY of the disease. Althoust:l some ear,lier investigat0rs fimke€l clemture stomatitis witlit trramma or Lflacte~ial infection, 0tt:lers had isolate€! Candida all!Jieams tr.0m the rnewtl;is 0f Ji)atients with tlfle G0Aditi!im. Current stw
While both methods of denture disinfection were successful, except for the counts of palatal aerobic bacteria, three independent observers of the clinical photographs had difficulty in identifying the controls but were more successful with the treatments. The raters also showed that there was no difference between both methods of disinfection and this agreed with the microbiological analysis.
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