Galaxies at the extremes: Ultra-diffuse galaxies in the Virgo Cluster

We report the discovery of three large (R29 >~ 1 arcminute) extremely low surface brightness (mu_(V,0) ~ 27.0) galaxies identified using our deep, wide-field imaging of the Virgo Cluster from the Burrell Schmidt telescope. Complementary data from the Next Generation Virgo Cluster Survey do not resolve red giant branch stars in these objects down to i=24, yielding a lower distance limit of 2.5 Mpc. At the Virgo distance, these objects have half-light radii 3-10 kpc and luminosities L_V=2-9x10^7 Lsun. These galaxies are comparable in size but lower in surface brightness than the large ultradiffuse LSB galaxies recently identified in the Coma cluster, and are located well within Virgo's virial radius; two are projected directly on the cluster core. One object appears to be a nucleated LSB in the process of being tidally stripped to form a new Virgo ultracompact dwarf galaxy. The others show no sign of tidal disruption, despite the fact that such objects should be most vulnerable to tidal destruction in the cluster environment. The relative proximity of Virgo makes these objects amenable to detailed studies of their structural properties and stellar populations. They thus provide an important new window onto the connection between cluster environment and galaxy evolution at the extremes.Comment: 7 pages, 4 figures, to appear in ApJ Letters. Updated with minor revisions to match accepted versio

Galaxies at the extremes: Ultra-diffuse galaxies in the Virgo Cluster

We report the discovery of three large (R29 >~ 1 arcminute) extremely low surface brightness (mu_(V,0) ~ 27.0) galaxies identified using our deep, wide-field imaging of the Virgo Cluster from the Burrell Schmidt telescope. Complementary data from the Next Generation Virgo Cluster Survey do not resolve red giant branch stars in these objects down to i=24, yielding a lower distance limit of 2.5 Mpc. At the Virgo distance, these objects have half-light radii 3-10 kpc and luminosities L_V=2-9x10^7 Lsun. These galaxies are comparable in size but lower in surface brightness than the large ultradiffuse LSB galaxies recently identified in the Coma cluster, and are located well within Virgo's virial radius; two are projected directly on the cluster core. One object appears to be a nucleated LSB in the process of being tidally stripped to form a new Virgo ultracompact dwarf galaxy. The others show no sign of tidal disruption, despite the fact that such objects should be most vulnerable to tidal destruction in the cluster environment. The relative proximity of Virgo makes these objects amenable to detailed studies of their structural properties and stellar populations. They thus provide an important new window onto the connection between cluster environment and galaxy evolution at the extremes.Comment: 7 pages, 4 figures, to appear in ApJ Letters. Updated with minor revisions to match accepted versio

Concentration dependence of translational diffusion coefficients for globular proteins

This investigation examines published results of traditional diffusion experiments on ovalbumin and bovine serum albumin to determine the extent to which assumed concentration independence of the translational diffusion coefficient is a reasonable approximation in the analysis of boundary spreading in sedimentation velocity experiments on proteins. Although significant positive concentration dependence of the diffusion coefficient (D) for both proteins is predicted by current theories, none has been detected in these experimental diffusion studies performed under the constraints of constant temperature and solvent chemical potential (those also pertinent to sedimentation velocity). Instead, the results are better described by the relatively minor concentration dependence predicted by considering solution viscosity to be an additional source of D–c dependence. Inasmuch as the predicted variation in D for solutions with concentrations below 10 mg mL-1 is within the uncertainty of experimental estimates, these findings support use of the approximate solution of the Lamm equation developed by Fujita for the quantitative analysis of boundary spreading in sedimentation velocity experiments on proteins

Association of immune response with efficacy and safety outcomes in adults with phenylketonuria administered pegvaliase in phase 3 clinical trials

Background: This study assessed the immunogenicity of pegvaliase (recombinant Anabaena variabilis phenylalanine [Phe] ammonia lyase [PAL] conjugated with polyethylene glycol [PEG]) treatment in adults with phenylketonuria (PKU) and its impact on safety and efficacy. Methods: Immunogenicity was assessed during induction, upward titration, and maintenance dosing regimens in adults with PKU (n = 261). Total antidrug antibodies (ADA), neutralizing antibodies, immunoglobulin (Ig) M and IgG antibodies against PAL and PEG, IgG and IgM circulating immune complex (CIC) levels, complement components 3 and 4 (C3/C4), plasma Phe, and safety were assessed at baseline and throughout the study. Pegvaliase-specific IgE levels were measured in patients after hypersensitivity adverse events (HAE). Findings: All patients developed ADA against PAL, peaking by 6 months and then stabilizing. Most developed transient antibody responses against PEG, peaking by 3 months, then returning to baseline by 9 months. Binding of ADA to pegvaliase led to CIC formation and complement activation, which were highest during early treatment. Blood Phe decreased over time as CIC levels and complement activation declined and pegvaliase dosage increased. HAEs were most frequent during early treatment and declined over time. No patient with acute systemic hypersensitivity events tested positive for pegvaliase-specific IgE near the time of the event. Laboratory evidence was consistent with immune complex-mediated type III hypersensitivity. No evidence of pegvaliase-associated IC-mediated end organ damage was noted. Interpretation: Despite a universal ADA response post-pegvaliase administration, adult patients with PKU achieved substantial and sustained blood Phe reductions with a manageable safety profile. Fund: BioMarin Pharmaceutical Inc. Keywords: Enzyme replacement therapy, Antidrug antibody, Circulating immune complex, Hypersensitivity, Phenylalanin

Quantifying the concentration dependence of sedimentation coefficients for globular macromolecules: a continuing age-old problem

This retrospective investigation has established that the early theoretical attempts to directly incorporate the consequences of radial dilution into expressions for variation of the sedimentation coefficient as a function of the loading concentration in sedimentation velocity experiments require concentration distributions exhibiting far greater precision than that achieved by the optical systems of past and current analytical ultracentrifuges. In terms of current methods of sedimentation coefficient measurement, until such improvement is made, the simplest procedure for quantifying linear s-c dependence (or linear concentration dependence of 1/s) for dilute systems therefore entails consideration of the sedimentation coefficient obtained by standard c(s), g*(s) or G(s) analysis) as an average parameter (s¯) that pertains to the corresponding mean plateau concentration (following radial dilution) (c¯) over the range of sedimentation velocity distributions used for the determination of s¯. The relation of this with current descriptions of the concentration dependence of the sedimentation and translational diffusion coefficients is considered, together with a suggestion for the necessary improvement in the optical system

Application of novel analytical ultracentrifuge analysis to solutions of fungal mannans

Polysaccharides, the most abundant biopolymers, are required for a host of activities in lower organisms, animals, and plants. Their solution characterization is challenging due to their complex shape, heterogeneity, and size. Here, recently developed data analysis approaches were applied for traditional sedimentation equilibrium and velocity methods in order to investigate the molar mass distribution(s) of a subtype of polysaccharide, namely, mannans from four Candida spp. The molecular weight distributions of these mannans were studied using two recently developed equilibrium approaches: SEDFIT-MSTAR and MULTISIG, resulting in corroboratory distribution profiles. Additionally, sedimentation velocity data for all four mannans, analyzed using ls-g*(s) and Extended Fujita approaches, suggest that two of the fungal mannans (FM-1 and FM-3) have a unimodal distribution of molecular species whereas two others (FM-2 and FM-4) displayed bi-modal and broad distributions, respectively: this demonstrates considerable molecular heterogeneity in these polysaccharides, consistent with previous observations of mannans and polysaccharides in general. These methods not only have applications for the characterization of mannans but for other biopolymers such as polysaccharides, DNA, and proteins (including intrinsically disordered proteins)