The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Manoel Manghi - One of the best experts on this subject based on the ideXlab platform.

  • dynamical control of Denaturation bubble nucleation in supercoiled DNA minicircles
    Physical Review E, 2020
    Co-Authors: Francois Sicard, Nicolas Destainville, Philippe Rousseau, Catherine Tardin, Manoel Manghi
    Abstract:

    We examine the behavior of supercoiled DNA minicircles containing between 200 and 400 base-pairs, also named microDNA, in which supercoiling favors thermally assisted DNA Denaturation bubbles of nanometer size and controls their lifetime. Mesoscopic modeling and accelerated dynamics simulations allow us to overcome the limitations of atomistic simulations encountered in such systems, and offer detailed insight into the thermodynamic and dynamical properties associated with the nucleation and closure mechanisms of long-lived thermally assisted Denaturation bubbles which do not stem from bending- or torque-driven stress. Suitable tuning of the degree of supercoiling and size of specifically designed microDNA is observed to lead to the control of opening characteristic times in the millisecond range, and closure characteristic times ranging over well distinct timescales, from microseconds to several minutes. We discuss how our results can be seen as a dynamical bandwidth which might enhance selectivity for specific DNA binding proteins.

  • DNA Denaturation bubbles free energy landscape and nucleation closure rates
    Journal of Chemical Physics, 2015
    Co-Authors: Francois Sicard, Nicolas Destainville, Manoel Manghi
    Abstract:

    The issue of the nucleation and slow closure mechanisms of non-superhelical stress-induced Denaturation bubbles in DNA is tackled using coarse-grained MetaDynamics and Brownian simulations. A minimal mesoscopic model is used where the double helix is made of two interacting bead-spring rotating strands with a prescribed torsional modulus in the duplex state. We demonstrate that timescales for the nucleation (respectively, closure) of an approximately 10 base-pair bubble, in agreement with experiments, are associated with the crossing of a free-energy barrier of 22 kBT (respectively, 13 kBT) at room temperature T. MetaDynamics allows us to reconstruct accurately the free-energy landscape, to show that the free-energy barriers come from the difference in torsional energy between the bubble and duplex states, and thus to highlight the limiting step, a collective twisting, that controls the nucleation/closure mechanism, and to access opening time scales on the millisecond range. Contrary to small breathing bubbles, those more than 4 base-pair bubbles are of biological relevance, for example, when a pre-existing state of Denaturation is required by specific DNA-binding proteins.

  • DNA Denaturation bubbles free energy landscape and nucleation closure rates
    arXiv: Soft Condensed Matter, 2014
    Co-Authors: Francois Sicard, Nicolas Destainville, Manoel Manghi
    Abstract:

    The issue of the nucleation and slow closure mechanisms of non superhelical stress-induced Denaturation bubbles in DNA is tackled using coarse-grained MetaDynamics and Brownian simulations. A minimal mesoscopic model is used where the double helix is made of two interacting bead-spring rotating strands with a prescribed torsional modulus in the duplex state. We demonstrate that timescales for the nucleation (resp. closure) of an approximately 10 base-pair bubble, in agreement with experiments, are associated with the crossing of a free-energy barrier of $22~k_{\rm B}T$ (resp. $13~k_{\rm B}T$) at room temperature $T$. MetaDynamics allows us to reconstruct accurately the free-energy landscape, to show that the free-energy barriers come from the difference in torsional energy between the bubble and duplex states, and thus to highlight the limiting step, a collective twisting, that controls the nucleation/closure mechanism, and to access opening time scales on the millisecond range. Contrary to small breathing bubbles, these more than 4~base-pair bubbles are of biological relevance, for example when a preexisting state of Denaturation is required by specific DNA-binding proteins.

Francois Sicard - One of the best experts on this subject based on the ideXlab platform.

  • dynamical control of Denaturation bubble nucleation in supercoiled DNA minicircles
    Physical Review E, 2020
    Co-Authors: Francois Sicard, Nicolas Destainville, Philippe Rousseau, Catherine Tardin, Manoel Manghi
    Abstract:

    We examine the behavior of supercoiled DNA minicircles containing between 200 and 400 base-pairs, also named microDNA, in which supercoiling favors thermally assisted DNA Denaturation bubbles of nanometer size and controls their lifetime. Mesoscopic modeling and accelerated dynamics simulations allow us to overcome the limitations of atomistic simulations encountered in such systems, and offer detailed insight into the thermodynamic and dynamical properties associated with the nucleation and closure mechanisms of long-lived thermally assisted Denaturation bubbles which do not stem from bending- or torque-driven stress. Suitable tuning of the degree of supercoiling and size of specifically designed microDNA is observed to lead to the control of opening characteristic times in the millisecond range, and closure characteristic times ranging over well distinct timescales, from microseconds to several minutes. We discuss how our results can be seen as a dynamical bandwidth which might enhance selectivity for specific DNA binding proteins.

  • DNA Denaturation bubbles free energy landscape and nucleation closure rates
    Journal of Chemical Physics, 2015
    Co-Authors: Francois Sicard, Nicolas Destainville, Manoel Manghi
    Abstract:

    The issue of the nucleation and slow closure mechanisms of non-superhelical stress-induced Denaturation bubbles in DNA is tackled using coarse-grained MetaDynamics and Brownian simulations. A minimal mesoscopic model is used where the double helix is made of two interacting bead-spring rotating strands with a prescribed torsional modulus in the duplex state. We demonstrate that timescales for the nucleation (respectively, closure) of an approximately 10 base-pair bubble, in agreement with experiments, are associated with the crossing of a free-energy barrier of 22 kBT (respectively, 13 kBT) at room temperature T. MetaDynamics allows us to reconstruct accurately the free-energy landscape, to show that the free-energy barriers come from the difference in torsional energy between the bubble and duplex states, and thus to highlight the limiting step, a collective twisting, that controls the nucleation/closure mechanism, and to access opening time scales on the millisecond range. Contrary to small breathing bubbles, those more than 4 base-pair bubbles are of biological relevance, for example, when a pre-existing state of Denaturation is required by specific DNA-binding proteins.

  • DNA Denaturation bubbles free energy landscape and nucleation closure rates
    arXiv: Soft Condensed Matter, 2014
    Co-Authors: Francois Sicard, Nicolas Destainville, Manoel Manghi
    Abstract:

    The issue of the nucleation and slow closure mechanisms of non superhelical stress-induced Denaturation bubbles in DNA is tackled using coarse-grained MetaDynamics and Brownian simulations. A minimal mesoscopic model is used where the double helix is made of two interacting bead-spring rotating strands with a prescribed torsional modulus in the duplex state. We demonstrate that timescales for the nucleation (resp. closure) of an approximately 10 base-pair bubble, in agreement with experiments, are associated with the crossing of a free-energy barrier of $22~k_{\rm B}T$ (resp. $13~k_{\rm B}T$) at room temperature $T$. MetaDynamics allows us to reconstruct accurately the free-energy landscape, to show that the free-energy barriers come from the difference in torsional energy between the bubble and duplex states, and thus to highlight the limiting step, a collective twisting, that controls the nucleation/closure mechanism, and to access opening time scales on the millisecond range. Contrary to small breathing bubbles, these more than 4~base-pair bubbles are of biological relevance, for example when a preexisting state of Denaturation is required by specific DNA-binding proteins.

Armand Zini - One of the best experts on this subject based on the ideXlab platform.

  • sperm nuclear histone h2b correlation with sperm DNA Denaturation and DNA stainability
    Asian Journal of Andrology, 2008
    Co-Authors: Armand Zini, Xiaoyang Zhang, Maria San Gabriel
    Abstract:

    Aim: To examine the relationship between sperm DNA damage and sperm nuclear histone (H2B) staining. Methods: We evaluated sperm samples from 14 consecutive asthenoteratozoospermic infertile men and six consecutive fertile controls. Sperm nuclear histone (H2B) staining and sperm chromatin integrity (assessed by sperm chromatin structure assay and expressed using the percentage of (i) DNA fragmentation index [%DFI] and (ii) high DNA stainability [%HDS)]) were evaluated. Results: Histone H2B immunocytochemistry demonstrated two nuclear staining patterns: (i) focal punctate staining; and (ii) diffuse staining. Infertile men had a higher mean percentage of spermatozoa exhibiting diffuse H2B staining than did fertile men (7.7% ± 4.6% vs. 1.6% ± 1.2%, respectively, P < 0.01). We observed significant relationships between the proportion of spermatozoa with diffuse nuclear histone staining and both sperm %DFI (r = 0.63, P < 0.01) and sperm %HDS (r = 0.63, P < 0.01). Conclusion: The data demonstrate that infertile men have a higher proportion of spermatozoa with diffuse histone H2B than do fertile men and suggest that sperm DNA damage might, at least in part, be due to abnormally high histone H2B levels. (Asian J Androl 2008 Nov; 10: 865–871)

  • potential adverse effect of sperm DNA damage on embryo quality after icsi
    Human Reproduction, 2005
    Co-Authors: Armand Zini, Keith Jarvi, James Meriano, Karim Kader, Carl A Laskin, Kenneth Cadesky
    Abstract:

    BACKGROUND: Sperm DNA damage is prevalent amongst infertile men and has been shown to strongly impact adversely natural reproduction, intrauterine insemination-assisted reproduction and to a lesser degree IVF/ICSI fertilization. The objective of this study was to examine further the relationship between sperm DNA Denaturation (DD) and reproductive outcomes after ICSI. METHODS: We evaluated infertile couples (n = 60) undergoing IVF/ICSI at a single centre. Sperm DD was assessed by flow cytometry analysis of Acridine Orange-treated sperm and expressed as the percentage of sperm with DD. Couples were sub-grouped according to sperm DD results: group 1: 0-15%; group 2: >15-30%; group 3: >30%. RESULTS: There were no differences between the three groups with regard to maternal age, sperm parameters, oocyte maturation, fertilization or pregnancy rates. Group 3 had a significantly higher rate of multinucleation among the embryo cohorts compared to either groups 1 or 2 (20% versus 10% and 8% respectively, P = 0.04). There was a statistically insignificant trend toward an increased spontaneous pregnancy loss rate in group 3 (P =0.50). CONCLUSION: Although we did not observe significant relationships between sperm DNA damage and either fertilization or pregnancy rates, the potential adverse effect of sperm DNA damage on embryo quality and spontaneous pregnancy loss is concerning.

  • beneficial effect of microsurgical varicocelectomy on human sperm DNA integrity
    Human Reproduction, 2005
    Co-Authors: Armand Zini, A. Blumenfeld, Jamie Libman, J Willis
    Abstract:

    BACKGROUND: Human sperm DNA damage may adversely affect reproductive outcomes, and the spermatozoa of infertile men possess substantially more DNA damage than that of fertile men. To date, there is no available treatment for men with high levels of sperm DNA damage. The objective of this study was to examine the effect of varicocelectomy on sperm DNA Denaturation (DD, an index of sperm DNA damage) in infertile men with a clinical varicocele. METHODS. We reviewed the reports of 37 men who underwent microsurgical varicocelectomy at our institution from September 2001 to July 2002. Standard semen parameters and the percentage of spermatozoa with DD (monitored by flow cytometry analysis of acridine orange-treated spermatozoa) were assessed before and 6 months after varicocelectomy. RESULTS. The percentage of spermatozoa with DD decreased following varicocelectomy compared with pre-operatively (27.7 versus 24.6%, respectively, P < 0.05). Sperm concentration and the percentages of motile sperm and normal forms (WHO criteria) increased following varicocelectomy, but the difference did not reach statistical significance. CONCLUSIONS. Our data suggest that varicocelectomy can improve human sperm DNA integrity in infertile men with varicocele. These data represent the first report of improved sperm DNA integrity after therapy and further support the beneficial effect of varicocelectomy on human spermatogenesis.

  • prevalence of abnormal sperm DNA Denaturation in fertile and infertile men
    Urology, 2002
    Co-Authors: Armand Zini, Donna Phang, Marc Anthony Fischer, Sharon Sharir, Bobby Shayegan, Keith Jarvi
    Abstract:

    Objectives. To examine the prevalence of abnormal sperm DNA Denaturation (DD), a marker of sperm DNA integrity, in a group of fertile and infertile men. Methods. Eighty-eight nonazoospermic, infertile men and 13 fertile men underwent standard semen analysis and acridine orange sperm DNA integrity studies. Standard semen parameters (sperm concentration, motility, and morphology) and sperm DNA integrity (expressed as the percentage of spermatozoa with DD) were measured. Results. Of the 88 infertile men, 13 had completely normal semen parameters and the remaining 75 had at least one abnormal semen parameter. The mean (SE) sperm DD level was significantly lower in the population of infertile men with normal semen parameters compared with those having abnormal parameters (11.1% 3.7% versus 23.1% 1.8%, respectively, P 0.001). Only 1 (8%) of the 13 men with normal semen parameters had elevated sperm DD (greater than 30%, verified on two separate analyses) compared with 13 (17%) of the 75 infertile men with abnormal semen parameters (P 0.05). None of the fertile controls had elevated sperm DD. We observed significant inverse correlations between the sperm DD and sperm motility, morphology, and concentration (P 0.001). Conclusions. Our data show that sperm DD negatively correlates with standard semen parameters and that an isolated abnormality of sperm DD, a marker of sperm DNA integrity, is uncommon in infertile men. Additional studies are needed to support the notion that isolated abnormalities of sperm DNA integrity may represent a new diagnosis for men with unexplained infertility. UROLOGY 60: 1069‐1072, 2002. © 2002, Elsevier Science Inc.

  • biologic variability of sperm DNA Denaturation in infertile men
    Urology, 2001
    Co-Authors: Armand Zini, Khaled M Kamal, Donna Phang, Jennifer Willis, Keith Jarvi
    Abstract:

    Abstract Objectives. To examine sperm DNA Denaturation (DD) in fertile and infertile men and assess the variability of conventional semen parameters and sperm DD in repeated semen samples from infertile men. Methods. Twenty-one consecutive nonazoospermic, infertile men each submitted two semen samples, 2 to 6 weeks apart. We examined semen samples from consecutive fertile men (n = 10) presenting for vasectomy as controls. Standard semen parameters (World Health Organization criteria) and sperm chromatin structure (evaluated by flow cytometry analysis of acridine orange-treated spermatozoa and expressed as the percentage of spermatozoa with denatured DNA) were monitored. Results. Fertile men had a significantly higher sperm concentration and percentage of sperm motility and a significantly lower percentage of sperm with DD than did infertile men (36 ± 5.2 × 10 6 /mL versus 12.5 ± 2.2 × 10 6 /mL, 60.0% ± 5.2% versus 30.1% ± 4.1%, and 8.9% ± 1.9% versus 20.3% ± 2.5%, respectively, P Conclusions. Our data demonstrate that infertile men have significantly higher sperm DD compared with fertile men and that sperm DD exhibits a low coefficient of variation (∼20%) on repeated assessment. These data suggest that sperm DD has a relatively low degree of biologic variability.

Nicolas Destainville - One of the best experts on this subject based on the ideXlab platform.

  • dynamical control of Denaturation bubble nucleation in supercoiled DNA minicircles
    Physical Review E, 2020
    Co-Authors: Francois Sicard, Nicolas Destainville, Philippe Rousseau, Catherine Tardin, Manoel Manghi
    Abstract:

    We examine the behavior of supercoiled DNA minicircles containing between 200 and 400 base-pairs, also named microDNA, in which supercoiling favors thermally assisted DNA Denaturation bubbles of nanometer size and controls their lifetime. Mesoscopic modeling and accelerated dynamics simulations allow us to overcome the limitations of atomistic simulations encountered in such systems, and offer detailed insight into the thermodynamic and dynamical properties associated with the nucleation and closure mechanisms of long-lived thermally assisted Denaturation bubbles which do not stem from bending- or torque-driven stress. Suitable tuning of the degree of supercoiling and size of specifically designed microDNA is observed to lead to the control of opening characteristic times in the millisecond range, and closure characteristic times ranging over well distinct timescales, from microseconds to several minutes. We discuss how our results can be seen as a dynamical bandwidth which might enhance selectivity for specific DNA binding proteins.

  • DNA Denaturation bubbles free energy landscape and nucleation closure rates
    Journal of Chemical Physics, 2015
    Co-Authors: Francois Sicard, Nicolas Destainville, Manoel Manghi
    Abstract:

    The issue of the nucleation and slow closure mechanisms of non-superhelical stress-induced Denaturation bubbles in DNA is tackled using coarse-grained MetaDynamics and Brownian simulations. A minimal mesoscopic model is used where the double helix is made of two interacting bead-spring rotating strands with a prescribed torsional modulus in the duplex state. We demonstrate that timescales for the nucleation (respectively, closure) of an approximately 10 base-pair bubble, in agreement with experiments, are associated with the crossing of a free-energy barrier of 22 kBT (respectively, 13 kBT) at room temperature T. MetaDynamics allows us to reconstruct accurately the free-energy landscape, to show that the free-energy barriers come from the difference in torsional energy between the bubble and duplex states, and thus to highlight the limiting step, a collective twisting, that controls the nucleation/closure mechanism, and to access opening time scales on the millisecond range. Contrary to small breathing bubbles, those more than 4 base-pair bubbles are of biological relevance, for example, when a pre-existing state of Denaturation is required by specific DNA-binding proteins.

  • DNA Denaturation bubbles free energy landscape and nucleation closure rates
    arXiv: Soft Condensed Matter, 2014
    Co-Authors: Francois Sicard, Nicolas Destainville, Manoel Manghi
    Abstract:

    The issue of the nucleation and slow closure mechanisms of non superhelical stress-induced Denaturation bubbles in DNA is tackled using coarse-grained MetaDynamics and Brownian simulations. A minimal mesoscopic model is used where the double helix is made of two interacting bead-spring rotating strands with a prescribed torsional modulus in the duplex state. We demonstrate that timescales for the nucleation (resp. closure) of an approximately 10 base-pair bubble, in agreement with experiments, are associated with the crossing of a free-energy barrier of $22~k_{\rm B}T$ (resp. $13~k_{\rm B}T$) at room temperature $T$. MetaDynamics allows us to reconstruct accurately the free-energy landscape, to show that the free-energy barriers come from the difference in torsional energy between the bubble and duplex states, and thus to highlight the limiting step, a collective twisting, that controls the nucleation/closure mechanism, and to access opening time scales on the millisecond range. Contrary to small breathing bubbles, these more than 4~base-pair bubbles are of biological relevance, for example when a preexisting state of Denaturation is required by specific DNA-binding proteins.

Ralf Metzler - One of the best experts on this subject based on the ideXlab platform.

  • single DNA Denaturation and bubble dynamics
    Journal of Physics: Condensed Matter, 2009
    Co-Authors: Ralf Metzler, Tobias Ambjornsson, Andreas Hanke, Hans C Fogedby
    Abstract:

    While the Watson–Crick double-strand is the thermodynamically stable state of DNA in a wide range of temperature and salt conditions, even at physiological conditions local Denaturation bubbles may open up spontaneously due to thermal activation. By raising the ambient temperature, titration, or by external forces in single molecule setups bubbles proliferate until full Denaturation of the DNA occurs. Based on the Poland–Scheraga model we investigate both the equilibrium transition of DNA Denaturation and the dynamics of the Denaturation bubbles with respect to recent single DNA chain experiments for situations below, at, and above the Denaturation transition. We also propose a new single molecule setup based on DNA constructs with two bubble zones to measure the bubble coalescence and extract the physical parameters relevant to DNA breathing. Finally we consider the interplay between Denaturation bubbles and selectively single-stranded DNA binding proteins.

  • Denaturation transition of stretched DNA
    Physical Review Letters, 2008
    Co-Authors: Andreas Hanke, Martha G Ochoa, Ralf Metzler
    Abstract:

    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 on why is the DNA Denaturation transition first order
    Physical Review Letters, 2003
    Co-Authors: Andreas Hanke, Ralf Metzler
    Abstract:

    In this comment we argue that while the conclusions in the original paper (Y. Kafri, D. Mukamel and L. Peliti, Phys. Rev. Lett. 85, 4988 (2000)) are correct for asymptotically long DNA chains, they do not apply to the chains used in typical experiments. In the added last paragraph, we point out that for real DNA the average distance between denatured loops is not of the order of the persistence length of a single-stranded chain but much larger. This corroborates our reasoning that the double helix between loops is quite rigid, and thereby our conclusion.