OTX015 Gives Brand-New Lifespan To An Old Problem. . . Defacto Primary

The most common method for viscosity analysis consists of using a capillary viscometer (e.g., an Ostwald viscometer) submerged in a temperature-controlled water bath, to compare the flow times of polymer solutions of different concentrations with that of pure solvents (under constant temperature, pressure and http://www.selleckchem.com/products/AG-014699.html volume). High molecular weight polymers have higher intrinsic viscosity than low molecular weight and/or linear polymers (Landel and Nielsen, 1993). Thus, viscosity measurements can be used to infer the molecular weight of polymers in solution. Until recently, most of what was known on capsule properties had been inferred from data on secreted PS recovered from culture supernatants (Cherniak et al., 1988), believed to represent shed capsular material. However, a comparison of secreted PS isolated by two different techniques with capsular PS stripped from cells using either gamma radiation or dimethyl sulfoxide (DMSO) treatment revealed significant differences in glycosyl composition, mass, size, charge, viscosity, circular-dichroism spectra, and monoclonal antibody reactivity (Frases et al., 2008), strongly suggesting that secreted PS and capsular PS are structurally different, and questioning the use of secreted PS as a surrogate for the capsule PS, in biochemical studies. Also, these data confirm that the extraction/isolation method may influence significantly the structural and antigenic properties of PS fractions (Nimrichter et al., 2007). Analysis of the size of capsule GXM molecules removed from cryptococcal cells by DMSO revealed a wide distribution, with average-molecular weights ranging from kilo- to mega-Daltons (McFadden et al., 2006, 2007). Also, these and other datasets highlight the considerable inter-strain variability in the properties of the cryptococcal capsular PS (Cherniak et al., 1988, 1995; McFadden et al., 2007). Macromolecular characterization of capsular PS from different cryptococcal strains shows that these molecules are particularly large, exhibiting weight-average molecular weights from 107 to 108 g mol�C1, molecular sizes ranging from 158 to 239 nm, and average hydrodynamic radius values ranging from 570 to 2434 nm, as determined by static and DLS. The high values of average molecular weight observed for capsular PS molecules are consistent with previous reports (Frases et al., 2008), and confirm a fundamental difference between capsular and secreted PS molecules, since the latter has average molecular weights from 105 to 106 g mol�C1 only (McFadden et al., 2006, 2007; Frases et al., 2008). To our knowledge, the cryptococcal capsular PS molecules are the largest PS molecules described to date.