43 research outputs found
Rotational averaging-out gravitational sedimentation of colloidal dispersions and phenomena
We report on the differences between colloidal systems left to evolve in the
earth's gravitational field and the same systems for which a slow continuous
rotation averaged out the effects of particle sedimentation on a distance scale
small compared to the particle size. Several systems of micron-sized colloidal
particles were studied: a hard sphere fluid, colloids interacting via
long-range electrostatic repulsions above the freezing volume fraction, an
oppositely charged colloidal system close to either gelation and/or
crystallization, colloids with a competing short-range depletion attraction and
a long-range electrostatic repulsion, colloidal dipolar chains, and colloidal
gold platelets under conditions where they formed stacks. Important differences
in the structure formation were observed between the experiments where the
particles were allowed to sediment and those where sedimentation was averaged
out. For instance, in the case of colloids interacting via long-range
electrostatic repulsions, an unusual sequence of
dilute-Fluid/dilute-Crystal/dense-Fluid/dense-Crystal phases was observed
throughout the suspension under the effect of gravity, related to the volume
fraction dependence of the colloidal interactions, whereas the system stayed
homogeneously crystallized with rotation. For the oppositely charged colloids,
a gel-like structure was found to collapse under the influence of gravity with
a few crystalline layers grown on top of the sediment, whereas when the
colloidal sedimentation was averaged out, the gel completely transformed into
crystallites that were oriented randomly throughout the sample. Rotational
averaging out gravitational sedimentation is an effective and cheap way to
estimate the importance of gravity for colloidal self-assembly processes.Comment: 13 pages, 13 figure
FMR1 premutation and full mutation molecular mechanisms related to autism
Fragile X syndrome (FXS) is caused by an expanded CGG repeat (>200 repeats) in the 5′ un-translated portion of the fragile X mental retardation 1 gene (FMR1) leading to a deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA-binding protein that regulates the translation of a number of other genes that are important for synaptic development and plasticity. Furthermore, many of these genes, when mutated, have been linked to autism in the general population, which may explain the high comorbidity that exists between FXS and autism spectrum disorders (ASD). Additionally, premutation repeat expansions (55 to 200 CGG repeats) may also give rise to ASD through a different molecular mechanism that involves a direct toxic effect of FMR1 mRNA. It is believed that RNA toxicity underlies much of the premutation-related involvement, including developmental concerns like autism, as well as neurodegenerative issues with aging such as the fragile X-associated tremor ataxia syndrome (FXTAS). RNA toxicity can also lead to mitochondrial dysfunction, which is common in older premutation carriers both with and without FXTAS. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in idiopathic autism. Research regarding dysregulation of neurotransmitter systems caused by the lack of FMRP in FXS, including metabotropic glutamate receptor 1/5 (mGluR1/5) pathway and GABA pathways, has led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism
Thermal Stability of the Human Immunodeficiency Virus Type 1 (HIV-1) Receptors, CD4 and CXCR4, Reconstituted in Proteoliposomes
BACKGROUND: The entry of human immunodeficiency virus (HIV-1) into host cells involves the interaction of the viral exterior envelope glycoprotein, gp120, and receptors on the target cell. The HIV-1 receptors are CD4 and one of two chemokine receptors, CCR5 or CXCR4. METHODOLOGY/PRINCIPAL FINDINGS: We created proteoliposomes that contain CD4, the primary HIV-1 receptor, and one of the coreceptors, CXCR4. Antibodies against CD4 and CXCR4 specifically bound the proteoliposomes. CXCL12, the natural ligand for CXCR4, and the small-molecule CXCR4 antagonist, AMD3100, bound the proteoliposomes with affinities close to those associated with the binding of these molecules to cells expressing CXCR4 and CD4. The HIV-1 gp120 exterior envelope glycoprotein bound tightly to proteoliposomes expressing only CD4 and, in the presence of soluble CD4, bound weakly to proteoliposomes expressing only CXCR4. The thermal stability of CD4 and CXCR4 inserted into liposomes was examined. Thermal denaturation of CXCR4 followed second-order kinetics, with an activation energy (E(a)) of 269 kJ/mol (64.3 kcal/mol) and an inactivation temperature (T(i)) of 56°C. Thermal inactivation of CD4 exhibited a reaction order of 1.3, an E(a) of 278 kJ/mol (66.5 kcal/mol), and a T(i) of 52.2°C. The second-order denaturation kinetics of CXCR4 is unusual among G protein-coupled receptors, and may result from dimeric interactions between CXCR4 molecules. CONCLUSIONS/SIGNIFICANCE: Our studies with proteoliposomes containing the native HIV-1 receptors allowed an examination of the binding of biologically important ligands and revealed the higher-order denaturation kinetics of these receptors. CD4/CXCR4-proteoliposomes may be useful for the study of virus-target cell interactions and for the identification of inhibitors
Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing
Possibilities and limitations of current technologies for quantification of biological extracellular vesicles and synthetic mimics
A microfluidic trap array for longitudinal monitoring and multi-modal phenotypic analysis of individual stem cell aggregates
Potential therapeutic interventions for fragile X syndrome
Fragile X syndrome (FXS) is caused by a lack of the fragile X mental retardation protein (FMRP); FMRP deficiency in neurons of patients with FXS causes intellectual disability (IQ<70) and several behavioural problems, including hyperactivity and autistic-like features. In the brain, no gross morphological malformations have been found, although subtle spine abnormalities have been reported. FXS has been linked to altered group I metabotropic glutamate receptor (mGluR)-dependent and independent forms of synaptic plasticity. Here, we discuss potential targeted therapeutic strategies developed to specifically correct disturbances in the excitatory mGl