216 research outputs found
Phase separation in mixtures of colloids and long ideal polymer coils
Colloidal suspensions with free polymer coils which are larger than the
colloidal particles are considered. The polymer-colloid interaction is modeled
by an extension of the Asakura-Oosawa model. Phase separation occurs into
dilute and dense fluid phases of colloidal particles when polymer is added. The
critical density of this transition tends to zero as the size of the polymer
coils diverges.Comment: 5 pages, 3 figure
Interfacial tension and nucleation in mixtures of colloids and long ideal polymer coils
Mixtures of ideal polymers with hard spheres whose diameters are smaller than
the radius of gyration of the polymer, exhibit extensive immiscibility. The
interfacial tension between demixed phases of these mixtures is estimated, as
is the barrier to nucleation. The barrier is found to scale linearly with the
radius of the polymer, causing it to become large for large polymers. Thus for
large polymers nucleation is suppressed and phase separation proceeds via
spinodal decomposition, as it does in polymer blends.Comment: 4 pages (v2 includes discussion of the scaling of the interfacial
tension along the coexistence curve and its relation to the Ginzburg
criterion
Beware of density dependent pair potentials
Density (or state) dependent pair potentials arise naturally from
coarse-graining procedures in many areas of condensed matter science. However,
correctly using them to calculate physical properties of interest is subtle and
cannot be uncoupled from the route by which they were derived. Furthermore,
there is usually no unique way to coarse-grain to an effective pair potential.
Even for simple systems like liquid Argon, the pair potential that correctly
reproduces the pair structure will not generate the right virial pressure.
Ignoring these issues in naive applications of density dependent pair
potentials can lead to an apparent dependence of thermodynamic properties on
the ensemble within which they are calculated, as well as other
inconsistencies. These concepts are illustrated by several pedagogical
examples, including: effective pair potentials for systems with many-body
interactions, and the mapping of charged (Debye-H\"{u}ckel) and uncharged
(Asakura-Oosawa) two-component systems onto effective one-component ones.Comment: 22 pages, uses iopart.cls and iopart10.clo; submitted to Journal of
Physics Condensed Matter, special issue in honour of professor Jean-Pierre
Hanse
Mutant ubiquitin found in neurodegenerative disorders is a ubiquitin fusion degradation substrate that blocks proteasomal degradation
Loss of neurons in neurodegenerative diseases is usually preceded by the accumulation of protein deposits that contain components of the ubiquitin/proteasome system. Affected neurons in Alzheimer's disease often accumulate UBB+1, a mutant ubiquitin carrying a 19–amino acid C-terminal extension generated by a transcriptional dinucleotide deletion. Here we show that UBB+1 is a potent inhibitor of ubiquitin-dependent proteolysis in neuronal cells, and that this inhibitory activity correlates with induction of cell cycle arrest. Surprisingly, UBB+1 is recognized as a ubiquitin fusion degradation (UFD) proteasome substrate and ubiquitinated at Lys29 and Lys48. Full blockade of proteolysis requires both ubiquitination sites. Moreover, the inhibitory effect was enhanced by the introduction of multiple UFD signals. Our findings suggest that the inhibitory activity of UBB+1 may be an important determinant of neurotoxicity and contribute to an environment that favors the accumulation of misfolded proteins
Quantitative Virus-Associated RNA Detection to Monitor Oncolytic Adenovirus Replication
Oncolytic adenoviruses are in development as immunotherapeutic agents for solid tumors. Their efficacy is in part dependent on their ability to replicate in tumors. It is, however, difficult to obtain evidence for intratumoral oncolytic adenovirus replication if direct access to the tumor is not possible. Detection of systemic adenovirus DNA, which is sometimes used as a proxy, has limited value because it does not distinguish between the product of intratumoral replication and injected virus that did not replicate. Therefore, we investigated if detection of virus-associated RNA (VA RNA) by RT-qPCR on liquid biopsies could be used as an alternative. We found that VA RNA is expressed in adenovirus-infected cells in a replication-dependent manner and is secreted by these cells in association with extracellular vesicles. This allowed VA RNA detection in the peripheral blood of a preclinical in vivo model carrying adenovirus-injected human tumors and on liquid biopsies from a human clinical trial. Our results confirm that VA RNA detection in liquid biopsies can be used for minimally invasive assessment of oncolytic adenovirus replication in solid tumors in vivo.</p
Influence of polymer excluded volume on the phase behavior of colloid-polymer mixtures
We determine the depletion-induced phase-behavior of hard sphere colloids and
interacting polymers by large-scale Monte Carlo simulations using very accurate
coarse-graining techniques. A comparison with standard Asakura-Oosawa model
theories and simulations shows that including excluded volume interactions
between polymers leads to qualitative differences in the phase diagrams. These
effects become increasingly important for larger relative polymer size. Our
simulations results agree quantitatively with recent experiments.Comment: 5 pages, 4 figures submitted to Physical Review Letter
A coil-globule transition of a semiflexible polymer driven by the addition of spherical particles
The phase behaviour of a single large semiflexible polymer immersed in a
suspension of spherical particles is studied. All interactions are simple
excluded volume interactions and the diameter of the spherical particles is an
order of magnitude larger than the diameter of the polymer. The spherical
particles induce a quite long ranged depletion attraction between the segments
of the polymer and this induces a continuous coil-globule transition in the
polymer. This behaviour gives an indication of the condensing effect of
macromolecular crowding on DNA.Comment: 12 pages, 4 figure
Structure of Colloid-Polymer Suspensions
We discuss structural correlations in mixtures of free polymer and colloidal
particles based on a microscopic, 2-component liquid state integral equation
theory. Whereas in the case of polymers much smaller than the spherical
particles the relevant polymer degree of freedom is the center of mass, for
polymers larger than the (nano-) particles conformational rearrangements need
to be considered. They have the important consequence that the polymer
depletion layer exhibits two widely different length scales, one of the order
of the particle radius, the other of the order of the polymer radius or the
polymer density screening length in dilute or semidilute concentrations,
respectively. Their consequences on phase stability and structural correlations
are discussed extensively.Comment: 37 pages, 17 figures; topical feature articl
Epigenetic characterization of the FMR1 promoter in induced pluripotent stem cells from human fibroblasts carrying an unmethylated full mutation
Silencing of the FMR1 gene leads to fragile X syndrome, the most common cause of inherited intellectual disability. To study the epigenetic modifications of the FMR1 gene during silencing in time, we used fibroblasts and induced pluripotent stem cells (iPSCs) of an unmethylated full mutation (uFM) individual with normal intelligence. The uFM fibroblast line carried an unmethylated FMR1 promoter region and expressed normal to slightly increased FMR1 mRNA levels. The FMR1 expression in the uFM line corresponds with the increased H3 acetylation and H3K4 methylation in combination with a reduced H3K9 methylation. After reprogramming, the FMR1 promoter region was methylated in all uFM iPSC clones. Two clones were analyzed further and showed a lack of FMR1 expression, whereas the presence of specific histone modifications also indicated a repressed FMR1 promoter. In conclusion, these findings demonstrate that the standard reprogramming procedure leads to epigenetic silencing of the fully mutated FMR1 gene
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