The Role of Cholesterol on Triterpenoid Saponin-Induced Endolysosomal Escape of a Saporin-Based Immunotoxin

Cholesterol seems to play a central role in the augmentation of saporin-based immunotoxin (IT) cytotoxicity by triterpenoid saponins. Endolysosomal escape has been proposed as one mechanism for the saponin-mediated enhancement of targeted toxins. We investigated the effects of lipid depletion followed by repletion on Saponinum album (SA)-induced endolysosomal escape of Alexa Fluor labelled saporin and the saporin-based immunotoxin OKT10-SAP, directed against CD38, in Daudi lymphoma cells. Lipid deprived cells showed reduced SA-induced endolysosomal escape at two concentrations of SA, as determined by a flow cytometric method. The repletion of membrane cholesterol by low density lipoprotein (LDL) restored SA-induced endolysosomal escape at a concentration of 5 µg/mL SA but not at 1 µg/mL SA. When LDL was used to restore the cholesterol levels in lipid deprived cells, the SA augmentation of OKT10-SAP cytotoxicity was partially restored at 1 µg/mL SA and fully restored at 5 µg/mL SA. These results suggest that different mechanisms of action might be involved for the two different concentrations of SA and that endosomal escape may not be the main mechanism for the augmentation of saporin IT cytotoxicity by SA at the sub-lytic concentration of 1 µg/mL SA.     

Space and competition

We review the argument that incorporating space in economic models has two important consequences: first, the hypothesis of perfect competition becomes untenable, and second, the distinction between private and public goods becomes blurred. We summarize recent work pointing to alternative incentive systems that might lead to efficient location decisions and pricing policies.     

Homelessness and social control: a typology

Abstract

The use of ‘social control’ interventions in housing and welfare policy often courts intense controversy, and never more so than when attempts are made to bring about change in the conduct of street homeless people. To date, academic scrutiny has focused on the so-called ‘regulation’ or ‘criminalisation’ of rough sleepers occupying public space, but a range of ‘softer’ control mechanisms are also now in evidence within homelessness support services. This paper explicates the relationship between the distinct forms of social control that have been used in this field – force, coercion, bargaining, influence and tolerance – and compares the perspectives of policy makers, frontline practitioners and homeless people regarding the appropriateness of their deployment in England. It emphasizes that the use of every one of these modes of social control, and indeed the absence of such controls, raises moral and practical dilemmas, the nuance of which is often unacknowledged in academic accounts.     

Relationship between persistent organic pollutants (POPs) and ranging patterns in common bottlenose dolphins (Tursiops truncatus) from coastal Georgia, USA

Bottlenose dolphins (Tursiops truncatus) are apex predators in coastal southeastern U.S. waters; as such they are indicators of persistent organic pollutants (POPs) in coastal ecosystems. POP concentrations measured in a dolphin's blubber are influenced by a number of factors, including the animal's sex and ranging pattern in relation to POP point sources. This study examined POP concentrations measured in bottlenose dolphin blubber samples (n = 102) from the Georgia, USA coast in relation to individual ranging patterns and specifically, distance of sightings from a polychlorinated biphenyl (PCB) point source near Brunswick, Georgia. Dolphin ranging patterns were determined based upon 5 years of photo-identification data from two field sites approximately 40 km apart: (1) the Brunswick field site, which included the Turtle/Brunswick River Estuary (TBRE), and (2) the Sapelo field site, which included the Sapelo Island National Estuarine Research Reserve (SINERR). Dolphins were categorized into one of three ranging patterns from photo-identification data. Individuals with sighting histories exclusively within one of the defined field sites were considered to have either Brunswick or Sapelo ranging patterns. Individuals sighted in both field sites were classified as having a Mixed ranging pattern. Brunswick males had the highest concentrations of PCBs reported for any marine mammal. The pattern of PCB congeners was consistent with Aroclor 1268, a highly chlorinated PCB mixture associated with a Superfund site in Brunswick. PCB levels in Sapelo males were lower than in Brunswick males, but comparable to the highest levels measured in other dolphin populations along the southeastern U.S. Female dolphins had higher Aroclor 1268 proportions than males, suggesting that the highly chlorinated congeners associated with Aroclor 1268 may not be offloaded through parturition and lactation, as easily as less halogenated POPs. Individuals sighted farther from the Superfund point source had lower Aroclor 1268 proportions.     

Metal concentrations in rural topsoil in South Carolina: potential for human health impact

Rural areas are often considered to have relatively uncontaminated soils; however few studies have measured metals in surface soil from low population areas. Many metals, i.e., arsenic (As), lead (Pb), and mercury (Hg), have well-documented negative neurological effects, and the developing fetus and young children are particularly at risk. Using a Medicaid database, two areas were identified: one with no increased prevalence of mental retardation and developmental delay (MR/DD) (Strip 1) and one with significantly higher prevalence of MR/DD (Strip 2) in children compared to the state-wide average. These areas were mapped and surface soil samples were collected from 0-5 cm depths from nodes of a uniform grid laid out across the sampling areas. Samples were analyzed for As, barium (Ba), beryllium (Be), chromium (Cr), copper (Cu), Pb, manganese (Mn), nickel (Ni), and Hg. Inverse distance weighting (IDW) was used to estimate concentrations throughout each strip area, and a principal component analysis (PCA) was used to identify common sources. All metal concentrations in Strip 2, the MR/DD cluster area, were significantly greater than those in Strip 1 and similar to those found in more urban and highly agricultural areas. Both Strips 1 and 2 had a high number of significant correlations between metals (33 for Strip 1 and 25 for Strip 2), suggesting possible similar natural or anthropogenic sources which was corroborated by PCA. While exposures were not assessed and direct causation between environmental soil metal concentrations and MR/DD cannot be concluded, the high metal concentrations in areas with an elevated prevalence of MR/DD warrants further consideration.     

Physicochemical Characterization of Polymer-Stabilized Coacervate Protocells

The bottom-up construction of cell mimics has produced a range of membrane-bound protocells that have been endowed with functionality and biochemical processes reminiscent of living systems. The contents of these compartments, however, experience semidilute conditions, whereas macromolecules in the cytosol exist in protein-rich, crowded environments that affect their physicochemical properties, such as diffusion and catalytic activity. Recently, complex coacervates have emerged as attractive protocellular models because their condensed interiors would be expected to mimic this crowding better. Here we explore some relevant physicochemical properties of a recently developed polymer-stabilized coacervate system, such as the diffusion of macromolecules in the condensed coacervate phase, relative to in dilute solutions, the buffering capacity of the core, the molecular organization of the polymer membrane, the permeability characteristics of this membrane towards a wide range of compounds, and the behavior of a simple enzymatic reaction. In addition, either the coacervate charge or the cargo charge is engineered to allow the selective loading of protein cargo into the coacervate protocells. Our in-depth characterization has revealed that these polymer-stabilized coacervate protocells have many desirable properties, thus making them attractive candidates for the investigation of biochemical processes in stable, controlled, tunable, and increasingly cell-like environments.     

A process explanation of the effects of institutional distance between parties in outsourced information systems development projects

Outsourced information systems development (OISD) projects are challenging endeavors, and the literature suggests differences between the parties involved as critical hinderers of such projects. Using institutional theory as a foundational theory, we propose a process explanation of the effects of differences between parties in OISD projects. Our explanation relies on the interaction of four components: (1) the IS development and project management institutional profiles of the parties involved; (2) the institutional distance between practices within these profiles; (3) instances of conflicting institutional demands when institutional distance becomes salient; and (4) the repertoire of institutional strategic responses available to parties to address those instances. We suggest that the constitutive elements of institutional distance and the degree to which parties envision their collaboration beyond the project at hand contribute to explaining the enactment of strategic responses. Accounting for the fact that practices, as well as the institutional logics that drive their enactment, may differ between parties, we make a theoretical contribution to the literature on OISD by building a fine-grained explanation of the effects of differences between parties in OISD projects.