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Biomedical subjects

A Lesne

Publications and source records attributed to A Lesne.

7 recordsLinked to original sources
PubMed2006

Chromatin fiber functional organization: some plausible models.

We here present a modeling study of the chromatin fiber functional organization. Multi-scale modeling is required to unravel the complex interplay between the fiber and the DNA levels. It suggests plausible scenarios, including both physical and biological aspects, for fiber condensation, its targeted decompaction, and transcription regulation. We conclude that a major role of the chromatin fiber structure might be to endow DNA with allosteric potentialities and to control DNA transactions by an epigenetic tuning of its mechanical and topological constraints.

Chromatin↗
PubMed2006

The chromatin regulatory code: beyond a histone code.

In this commentary on the contribution by Arndt Benecke in this issue, I discuss why the notion of "chromatin code" introduced and elaborated in this paper is to be preferred to that of "histone code". Speaking of a code as regards nucleosome conformation and histone tail post-translational modifications only makes sense within the chromatin fiber, where their physico-chemical features can be translated into regulatory programs at the genome level, by means of a complex, multi-level interplay with the fiber architecture and dynamics settled in the course of Evolution. In particular, this chromatin code presumably exploits allosteric transitions of the chromatin fiber. The chromatin structure dependence of its translation suggests two alternative modes of transcription initiation regulation, also proposed in the paper by A. Benecke in this issue for interpreting strikingly bimodal micro-array data.

Chromatin↗
PubMed2002

Intercalation and buckling instability of DNA linker within locked chromatin fiber.

The chromatin fiber is a complex of DNA and specific proteins called histones forming the first structural level of organization of eukaryotic chromosomes. In tightly organized chromatin fibers, the short segments of naked DNA linking the nucleosomes are strongly end constrained. Longitudinal thermal fluctuations in these linkers allow intercalative mode of protein binding. We show that mechanical constraints generated in the first stage of the binding process induce linker DNA buckling; buckling in turn modifies the binding energies and activation barriers and creates a force of decondensation at the chromatin fiber level. The unique structure and properties of DNA thus yield a novel physical mechanism of buckling instability that might play a key role in the regulation of gene expression.

Journal Article↗
PubMed2001

Chromatin: a tunable spring at work inside chromosomes.

This paper focuses on mechanical aspects of chromatin biological functioning. Within a basic geometric modeling of the chromatin assembly, we give a complete set of elastic constants (twist and bend persistence lengths, stretch modulus and twist-stretch coupling constant) of the so-called 30-nm chromatin fiber, in terms of DNA elastic properties and geometric properties of the fiber assembly. The computation naturally embeds the fiber within a current analytical model known as the "extensible wormlike rope," allowing a straightforward prediction of the force-extension curves. We show that these elastic constants are strongly sensitive to the linker length, up to 1 bp, or equivalently to its twist, and might locally reach very low values, yielding a highly flexible and extensible domain in the fiber. In particular, the twist-stretch coupling constant, reflecting the chirality of the chromatin fiber, exhibits steep variations, and sign changes when the linker length is varied. We argue that this tunable elasticity might be a key feature for chromatin function, for instance, in the initiation and regulation of transcription.

Biomechanical Phenomena↗
PubMedDate not supplied

[Pharmacokinetics of methotrexate and clinical response associated in the medical treatment of ectopic pregnancies].

Methotrexate (MTX) is used in the medical treatment of unruptured ectopic pregnancy. This drug is administered by intramuscular (IM) or intrasaccular (IS) injection under sonographic control. No data are available concerning the pharmacokinetics of MTX in this new indication. This study compares the two administration routes in 12 patients (21 to 37 years) taken as their own control and presenting with ectopic pregnancy (51 +/- 12 days of amenorrhea). Our aim was to compare the pharmacokinetic profile of MTX for each route to facilitate its use in the future. The initial level of hCG was 4.474 +/- 4.184 mIU/ml. Each patient firstly received 1 mg/kg of MTX intrasaccularly under vaginal sonography. The same dose was injected intramuscularly 48 hours later. The pharmacokinetic profiles of MTX after IS and IM administrations were determined after both injections during 48 hours. MTX serum levels were measured by Fluorescence Polarization Immuno Assay. Data were analyzed by model independent methods and compared by a Wilcoxon T test (p 0.01 was considered as significant). All the unruptured ectopic pregnancy were cured and the hCG serum levels were normalized (10 mIU/ml) in 37 +/- 18 days. After IM administration, AUC0-infinity is significantly (p 0.01) increased i.e., 15.1 +/- 4.1 mumol.h/l versus 11.2 +/- 4.8 after IS injection. T1/2 lambda z and MRT remained unchanged whatever the route is i.e., 11.3 +/- 4.9 h and 8.6 +/- 3.9 h (IS) versus 12.1 +/- 5.9 h and 7.3 +/- 1.8 h (IM). The decrement of AUC0-infinity 8 determined after IS injection might be the consequence of the capture of the MTX by the trophoblastic cells (target cells).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗