488 research outputs found
Cell-specific conditional deletion of interleukin-1 (IL-1) ligands and its receptors : a new toolbox to study the role of IL-1 in health and disease
The pro-inflammatory cytokine interleukin-1 (IL-1) plays a key role in many physiological processes and during the inflammatory and immune response to most common diseases. IL-1 exists as two agonists, IL-1α and IL-1β that bind to the only signaling IL-1 type 1 receptor (IL-1R1), while a second decoy IL-1 type 2 receptor (IL-1R2) binds both forms of IL-1 without inducing cell signaling. The field of immunology and inflammation research has, over the past 35 years, unraveled many mechanisms of IL-1 actions, through in vitro manipulation of the IL-1 system or by using genetically engineered mouse models that lack either member of the IL-1 family in ubiquitous constitutive manner. However, the limitation of global mouse knockout technology has significantly hampered our understanding of the precise mechanisms of IL-1 actions in animal models of disease. Here we report and review the recent generation of new conditional mouse mutants in which exons of Il1a, Il1b, Il1r1, and Il1r2 genes flanked by loxP sites (fl/fl) can be deleted in cell-/tissue-specific constitutive or inducible manner by Cre recombinase expression. Hence, IL-1αfl/fl, IL-1βfl/fl, IL-1R1fl/fl, and IL-1R2fl/fl mice constitute a new toolbox that will provide a step change in our understanding of the cell-specific role of IL-1 and its receptor in health and disease and the potential development of targeted IL-1 therapies
Density fluctuations and the structure of a nonuniform hard sphere fluid
We derive an exact equation for density changes induced by a general external
field that corrects the hydrostatic approximation where the local value of the
field is adsorbed into a modified chemical potential. Using linear response
theory to relate density changes self-consistently in different regions of
space, we arrive at an integral equation for a hard sphere fluid that is exact
in the limit of a slowly varying field or at low density and reduces to the
accurate Percus-Yevick equation for a hard core field. This and related
equations give accurate results for a wide variety of fields
Gel transitions in colloidal suspensions
The idealized mode coupling theory (MCT) is applied to colloidal systems
interacting via short-range attractive interactions of Yukawa form. At low
temperatures MCT predicts a slowing down of the local dynamics and ergodicity
breaking transitions. The nonergodicity transitions share many features with
the colloidal gel transition, and are proposed to be the source of gelation in
colloidal systems. Previous calculations of the phase diagram are complemented
with additional data for shorter ranges of the attractive interaction, showing
that the path of the nonergodicity transition line is then unimpeded by the
gas-liquid critical curve at low temperatures. Particular attention is given to
the critical nonergodicity parameters, motivated by recent experimental
measurements. An asymptotic model is developed, valid for dilute systems of
spheres interacting via strong short-range attractions, and is shown to capture
all aspects of the low temperature MCT nonergodicity transitions.Comment: 12 pages, LaTeX, 5 eps figures, uses ioplppt.sty, to appear in J.
Phys.: Condens. Matte
An automated method for analysis of flow characteristics of circulating particles from in vivo video microscopy
Theory and simulation of short-range models of globular protein solutions
We report theoretical and simulation studies of phase coexistence in model
globular protein solutions, based on short-range, central, pair potential
representations of the interaction among macro-particles. After reviewing our
previous investigations of hard-core Yukawa and generalised Lennard-Jones
potentials, we report more recent results obtained within a DLVO-like
description of lysozyme solutions in water and added salt. We show that a
one-parameter fit of this model based on Static Light Scattering and
Self-Interaction Chromatography data in the dilute protein regime, yields
demixing and crystallization curves in good agreement with experimental
protein-rich/protein-poor and solubility envelopes. The dependence of cloud and
solubility points temperature of the model on the ionic strength is also
investigated. Our findings highlight the minimal assumptions on the properties
of the microscopic interaction sufficient for a satisfactory reproduction of
the phase diagram topology of globular protein solutions.Comment: 17 pages, 8 figures, Proc. of Conference "Structural Arrest
Transitions in Colloidal Systems with Short-Range Attractions", Messina
(ITALY) 17-20 December 200
Genotoxic agents promote the nuclear accumulation of annexin A2: role of annexin A2 in mitigating DNA damage
Annexin A2 is an abundant cellular protein that is mainly localized in the cytoplasm and plasma membrane, however a small population has been found in the nucleus, suggesting a nuclear function for the protein. Annexin A2 possesses a nuclear export sequence (NES) and inhibition of the NES is sufficient to cause nuclear accumulation. Here we show that annexin A2 accumulates in the nucleus in response to genotoxic agents including gamma-radiation, UV radiation, etoposide and chromium VI and that this event is mediated by the nuclear export sequence of annexin A2. Nuclear accumulation of annexin A2 is blocked by the antioxidant agent N-acetyl cysteine (NAC) and stimulated by hydrogen peroxide (H2O2), suggesting that this is a reactive oxygen species dependent event. In response to genotoxic agents, cells depleted of annexin A2 show enhanced phospho-histone H2AX and p53 levels, increased numbers of p53-binding protein 1 nuclear foci and increased levels of nuclear 8-oxo-2'-deoxyguanine, suggesting that annexin A2 plays a role in protecting DNA from damage. This is the first report showing the nuclear translocation of annexin A2 in response to genotoxic agents and its role in mitigating DNA damage.Natural Sciences and Engineering Research Council of Canada (NSERC); European Union [PCOFUND-GA-2009-246542]; Foundation for Science and Technology of Portugal; Beatrice Hunter Cancer Research Institute; Terry Fox Foundationinfo:eu-repo/semantics/publishedVersio
The liquid-vapor interface of an ionic fluid
We investigate the liquid-vapor interface of the restricted primitive model
(RPM) for an ionic fluid using a density-functional approximation based on
correlation functions of the homogeneous fluid as obtained from the
mean-spherical approximation (MSA). In the limit of a homogeneous fluid our
approach yields the well-known MSA (energy) equation of state. The ionic
interfacial density profiles, which for the RPM are identical for both species,
have a shape similar to those of simple atomic fluids in that the decay towards
the bulk values is more rapid on the vapor side than on the liquid side. This
is the opposite asymmetry of the decay to that found in earlier calculations
for the RPM based on a square-gradient theory. The width of the interface is,
for a wide range of temperatures, approximately four times the second moment
correlation length of the liquid phase. We discuss the magnitude and
temperature dependence of the surface tension, and argue that for temperatures
near the triple point the ratio of the dimensionless surface tension and
critical temperature is much smaller for the RPM than for simple atomic fluids.Comment: 6 postscript figures, submitted to Phys. Rev.
Theoretical description of phase coexistence in model C60
We have investigated the phase diagram of the Girifalco model of C60
fullerene in the framework provided by the MHNC and the SCOZA liquid state
theories, and by a Perturbation Theory (PT), for the free energy of the solid
phase. We present an extended assessment of such theories as set against a
recent Monte Carlo study of the same model [D. Costa et al, J. Chem. Phys.
118:304 (2003)]. We have compared the theoretical predictions with the
corresponding simulation results for several thermodynamic properties. Then we
have determined the phase diagram of the model, by using either the SCOZA, or
the MHNC, or the PT predictions for one of the coexisting phases, and the
simulation data for the other phase, in order to separately ascertain the
accuracy of each theory. It turns out that the overall appearance of the phase
portrait is reproduced fairly well by all theories, with remarkable accuracy as
for the melting line and the solid-vapor equilibrium. The MHNC and SCOZA
results for the liquid-vapor coexistence, as well as for the corresponding
critical points, are quite accurate. All results are discussed in terms of the
basic assumptions underlying each theory. We have selected the MHNC for the
fluid and the first-order PT for the solid phase, as the most accurate tools to
investigate the phase behavior of the model in terms of purely theoretical
approaches. The overall results appear as a robust benchmark for further
theoretical investigations on higher order C(n>60) fullerenes, as well as on
other fullerene-related materials, whose description can be based on a
modelization similar to that adopted in this work.Comment: RevTeX4, 15 pages, 7 figures; submitted to Phys. Rev.
Nonergodicity transitions in colloidal suspensions with attractive interactions
The colloidal gel and glass transitions are investigated using the idealized
mode coupling theory (MCT) for model systems characterized by short-range
attractive interactions. Results are presented for the adhesive hard sphere and
hard core attractive Yukawa systems. According to MCT, the former system shows
a critical glass transition concentration that increases significantly with
introduction of a weak attraction. For the latter attractive Yukawa system, MCT
predicts low temperature nonergodic states that extend to the critical and
subcritical region. Several features of the MCT nonergodicity transition in
this system agree qualitatively with experimental observations on the colloidal
gel transition, suggesting that the gel transition is caused by a low
temperature extension of the glass transition. The range of the attraction is
shown to govern the way the glass transition line traverses the phase diagram
relative to the critical point, analogous to findings for the fluid-solid
freezing transition.Comment: 11 pages, 7 figures; to be published in Phys. Rev. E (1 May 1999
Phase equilibria and glass transition in colloidal systems with short-ranged attractive interactions. Application to protein crystallization
We have studied a model of a complex fluid consisting of particles
interacting through a hard core and a short range attractive potential of both
Yukawa and square-well form. Using a hybrid method, including a self-consistent
and quite accurate approximation for the liquid integral equation in the case
of the Yukawa fluid, perturbation theory to evaluate the crystal free energies,
and mode-coupling theory of the glass transition, we determine both the
equilibrium phase diagram of the system and the lines of equilibrium between
the supercooled fluid and the glass phases. For these potentials, we study the
phase diagrams for different values of the potential range, the ratio of the
range of the interaction to the diameter of the repulsive core being the main
control parameter. Our arguments are relevant to a variety of systems, from
dense colloidal systems with depletion forces, through particle gels,
nano-particle aggregation, and globular protein crystallization.Comment: 20 pages, 10 figure
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