56 research outputs found
Scaling in Complex Systems: Analytical Theory of Charged Pores
In this paper we find an analytical solution of the equilibrium ion
distribution for a toroidal model of a ionic channel, using the Perfect
Screening Theorem (PST). The ions are charged hard spheres, and are treated
using a variational Mean Spherical Approximation (VMSA) .
Understanding ion channels is still a very open problem, because of the many
exquisite tuning details of real life channels. It is clear that the electric
field plays a major role in the channel behaviour, and for that reason there
has been a lot of work on simple models that are able to provide workable
theories. Recently a number of interesting papers have appeared that discuss
models in which the effect of the geometry, excluded volume and non-linear
behaviour is considered.
We present here a 3D model of ionic channels which consists of a charged,
deformable torus with a circular or elliptical cross section, which can be flat
or vertical (close to a cylinder). Extensive comparisons to MC simulations were
performed.
The new solution opens new possibilities, such as studying flexible pores,
and water phase transformations inside the pores using an approach similar to
that used on flat crystal surfaces
miR449 Protects Airway Regeneration by Controlling AURKA/HDAC6-Mediated Ciliary Disassembly
Airway mucociliary regeneration and function are key players for airway defense and are impaired in chronic obstructive pulmonary disease (COPD). Using transcriptome analysis in COPD-derived bronchial biopsies, we observed a positive correlation between cilia-related genes and microRNA-449 (miR449). In vitro, miR449 was strongly increased during airway epithelial mucociliary differentiation. In vivo, miR449 was upregulated during recovery from chemical or infective insults. miR0449-/- mice (both alleles are deleted) showed impaired ciliated epithelial regeneration after naphthalene and Haemophilus influenzae exposure, accompanied by more intense inflammation and emphysematous manifestations of COPD. The latter occurred spontaneously in aged miR449-/- mice. We identified Aurora kinase A and its effector target HDAC6 as key mediators in miR449-regulated ciliary homeostasis and epithelial regeneration. Aurora kinase A is downregulated upon miR449 overexpression in vitro and upregulated in miR449-/- mouse lungs. Accordingly, imaging studies showed profoundly altered cilia length and morphology accompanied by reduced mucociliary clearance. Pharmacological inhibition of HDAC6 rescued cilia length and coverage in miR449-/- cells, consistent with its tubulin-deacetylating function. Altogether, our study establishes a link between miR449, ciliary dysfunction, and COPD pathogenesis
miR449 Protects Airway Regeneration by Controlling AURKA/HDAC6-Mediated Ciliary Disassembly
Airway mucociliary regeneration and function are key players for airway defense and
are impaired in chronic obstructive pulmonary disease (COPD). Using transcriptome analysis in
COPD-derived bronchial biopsies, we observed a positive correlation between cilia-related genes
and microRNA-449 (miR449). In vitro, miR449 was strongly increased during airway epithelial
mucociliary differentiation. In vivo, miR449 was upregulated during recovery from chemical or
infective insults. miR0449−/− mice (both alleles are deleted) showed impaired ciliated epithelial
regeneration after naphthalene and Haemophilus influenzae exposure, accompanied by more intense
inflammation and emphysematous manifestations of COPD. The latter occurred spontaneously
in aged miR449−/− mice. We identified Aurora kinase A and its effector target HDAC6 as key
mediators in miR449-regulated ciliary homeostasis and epithelial regeneration. Aurora kinase A is
downregulated upon miR449 overexpression in vitro and upregulated in miR449−/− mouse lungs.
Accordingly, imaging studies showed profoundly altered cilia length and morphology accompanied
by reduced mucociliary clearance. Pharmacological inhibition of HDAC6 rescued cilia length and
coverage in miR449−/− cells, consistent with its tubulin-deacetylating function. Altogether, our study
establishes a link between miR449, ciliary dysfunction, and COPD pathogenesis
Frequency of Fibroblast Growth Factor Receptor 1 gene amplification in oral tongue squamous cell carcinomas and associations with clinical features and patient outcome
C1 - Journal Articles Referee
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