“
“α-Synuclein has been linked to the pathogenesis of Parkinson’s disease and other synucleinopathies through its propensity to form toxic oligomers. The exact mechanism for oligomeric synuclein-directed ICG-001 cell vulnerability has not been fully elucidated, but one hypothesis portends the formation of synuclein-containing pores within cell membranes leading to leak channel-mediated calcium influx and subsequent cell death. Here we demonstrate synuclein-induced formation of sodium dodecyl sulfate-stable oligomers, intracellular synuclein-positive aggregates, alterations

in membrane conductance reminiscent of leak channels and subsequent cytotoxicity in a dopaminergic-like cell line. Furthermore we demonstrate Selleck PD0325901 that the synuclein-induced membrane conductance changes are blocked by direct extracellular application of an anti-synuclein antibody. The work presented here confirms that synuclein overexpression leads to membrane conductance changes and demonstrates for the first time through antibody-blocking studies that synuclein plays a direct role in the formation of leak channels. “
“Pseudomonas aeruginosa produces and secretes several lipolytic enzymes, among them the lipases LipA and LipC. LipA is encoded within the lipA/lipH operon, together with its cognate foldase LipH, which was also found to be required for the functional expression of LipC. At present, the

physiological function of LipC is unknown. We have cloned a synthetic operon consisting of the lipC structural gene and the foldase gene lipH obtained from the lipA/lipH operon and have constructed, in parallel,

a lipC-deficient P. aeruginosa mutant. Inactivation of the lipC gene significantly impaired type IV pilus-dependent twitching and swarming motility, but also the flagella-mediated swimming motility of P. aeruginosa. Moreover, for the lipC mutant, we observed a significant decrease in the amount of extracellular rhamnolipids. Also, the P. aeruginosa lipC mutant showed a significantly altered biofilm architecture. Proteome analysis revealed the accumulation of the response regulator protein PhoP in the lipC mutant. Pseudomonas aeruginosa is a Gram-negative bacterium found in almost every ecological niche. As an opportunistic pathogen, it PIK-5 can infect different hosts including plants, nematodes, insects, amoeba and animals (Mahajan-Miklos et al., 2000; Rahme et al., 2000; Cosson et al., 2002). In humans, it causes serious infections, preferentially in immunocompromised individuals such as HIV patients or patients suffering from cystic fibrosis or severe burn wounds (Kirisits & Parsek, 2006). Biofilm formation is an important life style of P. aeruginosa and has been shown to be dependent in some aspects on flagella- and type IV pili-mediated motility (O’Toole & Kolter, 1998). Flagella-dependent swimming is coordinated by a classical chemotaxis system (Masduki et al., 1995; Kato et al., 1999).