438 research outputs found
Unfolding and unzipping of single-stranded DNA by stretching
We present a theoretical study of single-stranded DNA under stretching.
Within the proposed framework, the effects of basepairing on the mechanical
response of the molecule can be studied in combination with an arbitrary
underlying model of chain elasticity. In a generic case, we show that the
stretching curve of ssDNA exhibits two distinct features: the second-order
"unfolding" phase transition, and a sharp crossover, reminiscent of the
first-order "unzipping" transition in dsDNA. We apply the theory to the
particular cases of Worm-like Chain (WLC) and Freely-Joint Chain (FJC) models,
and discuss the universal and model--dependent features of the mechanical
response of ssDNA. In particular, we show that variation of the width of the
unzipping crossover with interaction strength is very sensitive to the
energetics of hairpin loops. This opens a new way of testing the elastic
properties of ssDNA.Comment: 7 pages, 4 figures, substantially revised versio
Getting DNA twist rigidity from single molecule experiments
We use an elastic rod model with contact to study the extension versus
rotation diagrams of single supercoiled DNA molecules. We reproduce
quantitatively the supercoiling response of overtwisted DNA and, using
experimental data, we get an estimation of the effective supercoiling radius
and of the twist rigidity of B-DNA. We find that unlike the bending rigidity,
the twist rigidity of DNA seems to vary widely with the nature and
concentration of the salt buffer in which it is immerged
Balancing torques in membrane-mediated interactions: Exact results and numerical illustrations
Torques on interfaces can be described by a divergence-free tensor which is
fully encoded in the geometry. This tensor consists of two terms, one
originating in the couple of the stress, the other capturing an intrinsic
contribution due to curvature. In analogy to the description of forces in terms
of a stress tensor, the torque on a particle can be expressed as a line
integral along any contour surrounding the particle. Interactions between
particles mediated by a fluid membrane are studied within this framework. In
particular, torque balance places a strong constraint on the shape of the
membrane. Symmetric two-particle configurations admit simple analytical
expressions which are valid in the fully nonlinear regime; in particular, the
problem may be solved exactly in the case of two membrane-bound parallel
cylinders. This apparently simple system provides some flavor of the remarkably
subtle nonlinear behavior associated with membrane-mediated interactions.Comment: 16 pages, 10 figures, REVTeX4 style. The Gaussian curvature term was
included in the membrane Hamiltonian; section II.B was rephrased to smoothen
the flow of presentatio
Novel amino-β-lactam derivatives as potent cholesterol absorption inhibitors
Two new trans-(3R, 4R)-amino-β-lactam derivatives and their diastereoisomeric mixtures were synthesized as ezetimibe bioisosteres and tested in in vitro and in vivo experiments as novel β-lactam cholesterol absorption inhibitors. Both compounds exhibited low cytotoxicity in MDCKII, hNPC1L1/MDCKII, and HepG2 cell lines and potent inhibitory effect in hNPC1L1/MDCKII cells. In addition, these compounds markedly reduced cholesterol absorption in mice, resulting in reduced cholesterol concentrations in plasma, liver, and intestine. We determined the crystal structure of one amino-β-lactam derivative to establish unambiguously both the absolute and relative configuration at the new stereogenic centre C17, which was assigned to be S. The pKa values for both compounds are 9.35, implying that the amino-β-lactam derivatives and their diastereoisomeric mixtures are in form of ammonium salt in blood and the intestine. The IC50 value for the diastereoisomeric mixture is 60 μM. In vivo, it efficiently inhibited cholesterol absorption comparable to ezetimibe
Conformational transitions of heteropolymers in dilute solutions
In this paper we extend the Gaussian self-consistent method to permit study
of the equilibrium and kinetics of conformational transitions for
heteropolymers with any given primary sequence. The kinetic equations earlier
derived by us are transformed to a form containing only the mean squared
distances between pairs of monomers. These equations are further expressed in
terms of instantaneous gradients of the variational free energy. The method
allowed us to study exhaustively the stability and conformational structure of
some periodic and random aperiodic sequences. A typical phase diagram of a
fairly long amphiphilic heteropolymer chain is found to contain phases of the
extended coil, the homogeneous globule, the micro-phase separated globule, and
a large number of frustrated states, which result in conformational phases of
the random coil and the frozen globule. We have also found that for a certain
class of sequences the frustrated phases are suppressed. The kinetics of
folding from the extended coil to the globule proceeds through non-equilibrium
states possessing locally compacted, but partially misfolded and frustrated,
structure. This results in a rather complicated multistep kinetic process
typical of glassy systems.Comment: 15 pages, RevTeX, 20 ps figures, accepted for publication in Phys.
Rev.
Novel role of a triglyceride-synthesizing enzyme:DGAT1 at the crossroad between triglyceride and cholesterol metabolism
AbstractAcyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in triacylglycerol (TG) biosynthesis. Here we show that genetic deficiency and pharmacological inhibition of DGAT1 in mice alters cholesterol metabolism. Cholesterol absorption, as assessed by acute cholesterol uptake, was significantly decreased in the small intestine and liver upon DGAT1 deficiency/inhibition. Ablation of DGAT1 in the intestine (I-DGAT1−/−) alone is sufficient to cause these effects. Consequences of I-DGAT1 deficiency phenocopy findings in whole-body DGAT1−/− and DGAT1 inhibitor-treated mice. We show that deficiency/inhibition of DGAT1 affects cholesterol metabolism via reduced chylomicron size and increased trans-intestinal cholesterol excretion. These effects are independent of cholesterol uptake at the apical surface of enterocytes but mediated through altered dietary fatty acid metabolism. Our findings provide insight into a novel role of DGAT1 and identify a pathway by which intestinal DGAT1 deficiency affects whole-body cholesterol homeostasis in mice. Targeting intestinal DGAT1 may represent a novel approach for treating hypercholesterolemia
The QCD Phase Structure at High Baryon Density
We consider the possibility that color deconfinement and chiral symmetry
restoration do not coincide in dense baryonic matter at low temperature. As a
consequence, a state of massive "constituent" quarks would exist as an
intermediate phase between confined nuclear matter and the plasma of deconfined
massless quarks and gluons. We discuss the properties of this state and its
relation to the recently proposed quarkyonic matter.Comment: 17 pages, 9 figure
Equation of state for polymer liquid crystals: theory and experiment
The first part of this paper develops a theory for the free energy of
lyotropic polymer nematic liquid crystals. We use a continuum model with
macroscopic elastic moduli for a polymer nematic phase. By evaluating the
partition function, considering only harmonic fluctuations, we derive an
expression for the free energy of the system. We find that the configurational
entropic part of the free energy enhances the effective repulsive interactions
between the chains. This configurational contribution goes as the fourth root
of the direct interactions. Enhancement originates from the coupling between
bending fluctuations and the compressibility of the nematic array normal to the
average director. In the second part of the paper we use osmotic stress to
measure the equation of state for DNA liquid crystals in 0.1M to 1M NaCl
solutions. These measurements cover 5 orders of magnitude in DNA osmotic
pressure. At high osmotic pressures the equation of state, dominated by
exponentially decaying hydration repulsion, is independent of the ionic
strength. At lower pressures the equation of state is dominated by fluctuation
enhanced electrostatic double layer repulsion. The measured equation of state
for DNA fits well with our theory for all salt concentrations. We are able to
extract the strength of the direct electrostatic double layer repulsion. This
is a new and alternative way of measuring effective charge densities along
semiflexible polyelectrolytes.Comment: text + 5 figures. Submitted to PR
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