Dynamics of DNA-breathing: Weak noise analysis, finite time singularity, and mapping onto the quantum Coulomb problem

We study the dynamics of denaturation bubbles in double-stranded DNA on the basis of the Poland-Scheraga model. We show that long time distributions for the survival of DNA bubbles and the size autocorrelation function can be derived from an asymptotic weak noise approach. In particular, below the melting temperature the bubble closure corresponds to a noisy finite time singularity. We demonstrate that the associated Fokker-Planck equation is equivalent to a quantum Coulomb problem. Below the melting temperature the bubble lifetime is associated with the continuum of scattering states of the repulsive Coulomb potential; at the melting temperature the Coulomb potential vanishes and the underlying first exit dynamics exhibits a long time power law tail; above the melting temperature, corresponding to an attractive Coulomb potential, the long time dynamics is controlled by the lowest bound state. Correlations and finite size effects are discussed.Comment: 12 pages, 10 figures, revte

Denaturation transition of stretched DNA

We generalize the Poland-Scheraga model to consider DNA denaturation in the presence of an external stretching force. We demonstrate the existence of a force-induced DNA denaturation transition and obtain the temperature-force phase diagram. The transition is determined by the loop exponent $c$ for which we find the new value $c=4\nu-1/2$ such that the transition is second order with $c=1.85<2$ in $d=3$. We show that a finite stretching force $F$ destabilizes DNA, corresponding to a lower melting temperature $T(F)$, in agreement with single-molecule DNA stretching experiments.Comment: 5 pages, 3 figure

Polyhedral vesicles

Polyhedral vesicles with a large bending modulus of the membrane such as the gel phase lipid membrane were studied using a Brownian dynamics simulation. The vesicles exhibit various polyhedral morphologies such as tetrahedron and cube shapes. We clarified two types of line defects on the edges of the polyhedrons: cracks of both monolayers at the spontaneous curvature of monolayer $C_{\text {0}}<0$, and a crack of the inner monolayer at $C_{\text {0}}\ge0$. Around the latter defect, the inner monolayer curves positively. Our results suggested that the polyhedral morphology is controlled by $C_{\text {0}}$.Comment: 4 pages, 5 figure

Associations between First Year Medical Students’ Lifestyles, Resting Blood Pressure, and Resting ECGs

Introduction: There is considerable evidence that psychological stressors can impact cardiovascular health. Medical students experience a high degree of stress based upon their responses to survey questionnaires, although there are few physiological studies that support this association that are targeted specifically to medical students. Medical students in general represent an underrepresented age group in the context of cardiovascular treatment guidelines. Therefore, medical students are a pertinent cohort for study based upon these findings. Objective:The purpose of this study was to analyze whether medical student lifestyles impact normal baseline cardiovascular measurements of blood pressures and electrocardiograms in this population. Methods: Twenty five Medical students in the Philadelphia College of Osteopathic Medicine graduating class of 2017 were recruited and met inclusion criteria. Blood pressure and lifestyle factor surveys were obtained on a weekly basis and ECGs were recorded biweekly. All ECGs were read by a cardiologist. Participation by the cardiologist and the subjects was voluntary and without compensation. BP and Heart Rate data were statistically analyzed using ANOVA and the ECG analyses using Fisher Exact Test. Data obtained throughout the study was compared to the subjects’ initial data gathered at the beginning of the academic year. Data was organized into the male gender category, the female gender category, and a category that combined the data for both genders. Results: There were statistically significant differences in the amount of caffeine consumption and systolic BP abnormalities (p=0.05), and also a statistically significant difference in the amount of strength training exercise and diastolic BP abnormalities (p=0.04) for the male gender category. There were statistically significant differences in the amount of strength training exercise and prevalence of early repolarization (p=0.01), and the amount of study hours and bradycardia (p= 0.04) for the female gender category.There were statistically significant differences between the amount of aerobic exercise and T wave inversions (p=0.03), anxiety level and voltage criteria for left ventricular hypertrophy (p=0.05), the amount of strength exercise and systolic BP abnormalities (p=0.02), the amount of strength exercise and diastolic abnormalities (p=0.004), the amount of study hours and bradycardia (p=0.034), and the amount of study hours and inverted T waves (p=0.008) for the combined gender category. Conclusion: Changes in both blood pressure and ECGs in association with both behavioral and curriculum lifestyle factors were demonstrated. Whether the behavioral habits that differed significantly from baseline were due to the curriculum cannot be determined from these preliminary analyses. However, these findings in this population are concerning with respect to younger adults as a discrete and unique population, and may warrant closer scrutiny in conjunction with the American Heart Association Guidelines to determine whether a new category of recommendations for younger adults may be warranted with respect to blood pressure and heart rate parameters

Master equation approach to DNA-breathing in heteropolymer DNA

After crossing an initial barrier to break the first base-pair (bp) in double-stranded DNA, the disruption of further bps is characterized by free energies between less than one to a few kT. This causes the opening of intermittent single-stranded bubbles. Their unzipping and zipping dynamics can be monitored by single molecule fluorescence or NMR methods. We here establish a dynamic description of this DNA-breathing in a heteropolymer DNA in terms of a master equation that governs the time evolution of the joint probability distribution for the bubble size and position along the sequence. The transfer coefficients are based on the Poland-Scheraga free energy model. We derive the autocorrelation function for the bubble dynamics and the associated relaxation time spectrum. In particular, we show how one can obtain the probability densities of individual bubble lifetimes and of the waiting times between successive bubble events from the master equation. A comparison to results of a stochastic Gillespie simulation shows excellent agreement.Comment: 12 pages, 8 figure

Bubble coalescence in breathing DNA: Two vicious walkers in opposite potentials

We investigate the coalescence of two DNA-bubbles initially located at weak segments and separated by a more stable barrier region in a designed construct of double-stranded DNA. The characteristic time for bubble coalescence and the corresponding distribution are derived, as well as the distribution of coalescence positions along the barrier. Below the melting temperature, we find a Kramers-type barrier crossing behaviour, while at high temperatures, the bubble corners perform drift-diffusion towards coalescence. The results are obtained by mapping the bubble dynamics on the problem of two vicious walkers in opposite potentials.Comment: 7 pages, 4 figure

Polymer reptation and nucleosome repositioning

We consider how beads can diffuse along a chain that wraps them, without becoming displaced from the chain; our proposed mechanism is analogous to the reptation of "stored length" in more familiar situations of polymer dynamics. The problem arises in the case of globular aggregates of proteins (histones) that are wound by DNA in the chromosomes of plants and animals; these beads (nucleosomes) are multiply wrapped and yet are able to reposition themselves over long distances, while remaining bound by the DNA chain.Comment: 9 pages, including 2 figures, to be published in Phys. Rev. Let

Nucleosome repositioning via loop formation

Active (catalysed) and passive (intrinsic) nucleosome repositioning is known to be a crucial event during the transcriptional activation of certain eucaryotic genes. Here we consider theoretically the intrinsic mechanism and study in detail the energetics and dynamics of DNA-loop-mediated nucleosome repositioning, as previously proposed by Schiessel et al. (H. Schiessel, J. Widom, R. F. Bruinsma, and W. M. Gelbart. 2001. {\it Phys. Rev. Lett.} 86:4414-4417). The surprising outcome of the present study is the inherent nonlocality of nucleosome motion within this model -- being a direct physical consequence of the loop mechanism. On long enough DNA templates the longer jumps dominate over the previously predicted local motion, a fact that contrasts simple diffusive mechanisms considered before. The possible experimental outcome resulting from the considered mechanism is predicted, discussed and compared to existing experimental findings