38 research outputs found
Bifurcations of equilibria in DNA elasticity
No full textDNA molecules in the familiar double helical B form are treated here as though they have rod-like structures obtained by stacking the
nearly planar base pairs comprising them one on top of another with each rotated by approximately one-tenth of a full turn with respect
to its immediate predecessor in the stack. As each base in a base pair is attached to the sugar-phosphate backbone chain of one of the
two DNA strands that have come together to form the Watson-Crick structure, and each phosphate group in a backbone chain bears one electronic charge, two such charges are associated with each base pair. Thus, each base pair is subject to not only the elastic forces and moments exerted on it by its neighboring base pairs but also to remote electrostatic forces that, because they are only partially screened out by positively charged counter ions, can render the molecule's equilibrium configurations sensitive to changes in the concentration c of salt in the medium.
The observation that the step from one base pair to the next can be one of several distinct types, each having its own mechanical properties that depend on the nucleotide composition of the step, and the assumption that a base pair is rigid, led to the development of a theory of sequence dependent DNA elasticity [Coleman, Olson, and Swigon, J. Chem. Phys. 118 ,7127-7140, (2003)]. The theory of DNA molecules in aqueous solution developed here is based on but goes beyond that theory. It takes into account the intramolecular electrostatic interactions of the negatively charged phosphate groups in the molecule and the impenetrability of the DNA molecule for cases in which the
electrostatic repulsive forces do not suffice to avoid self penetration. The theory permits one to calculate equilibrium configurations, to determine their stability, and to study the dependence of them on salt concentration and on all kinds of end conditions.
When the intramolecular electrostatic forces are taken into account, the equations of mechanical equilibrium for a DNA molecule with N+1 base pairs are a system of mu*N non-linear equations, where mu, the number of kinematical variables describing the relative displacement and orientation of adjacent base pairs is in general 6; it reduces to 3 when base-pair steps are assumed to be inextensible and non-shearable. An efficient numerically stable computational scheme is here presented for
solving those equations and determining the mechanical stability of the calculated equilibrium configurations. That scheme is employed to compute and analyze bifurcation diagrams in which c is the bifurcation parameter and to show that, for an intrinsically curved molecule, small changes in c can have a strong effect on stable
equilibrium configurations. Cases are presented in which self-contact must be taken into account even though the intramolecular electrostatic forces of repulsion are strong.Ph.D.Includes bibliographical references (p. 106-110)
LAMENTATIONS D’UN PATRIARCHISTE : ANALYSE D’AH ! LES FEMMES… D’ISAÏE BITON KOULIBALY COMME UNE RÉPLIQUE AUX ÉCRITS FEMINISTES
No full textThe French-language novel of Black Africa is characterised by an abundance of women\u27s literature, in which men are often presented as the main oppressors of women. In most of these works, men are vilified, blamed and held responsible for the subaltern, oppressed and submissive condition of women. These black women writers denounce patriarchy as a system that perpetuates the inferiorisation and marginalisation of women. In this context, this article argues that Isaïe Biton Koulibaly\u27s collection of short stories, Ah! Les femmes, is a response to African feminist narratives. Its main aim is to absolve men of any guilt while highlighting women\u27s shortcomings, both in the marital sphere and beyond. By focusing on patriarchy as a starting point, we show that the short stories in Ah! Les femmes... are a pretext for arguing for the return of patriarchy. The author seems to illustrate, through her short stories that African women are irredeemably flawed and therefore undeserving of the privileges they enjoy in contemporary Africa. Through the author\u27s work, it is clear that there is a desire to restore the retrograde patriarchal ideology, a system vigorously opposed by African feminist activists in their writings. It is concluded that writers, both men and women, should give priority to promoting gender complementarity in their works rather than adopting partisan positions.
Résumé Le roman francophone d’Afrique noire se caractérise par une production littéraire féminine foisonnante, où l’homme est souvent présenté comme le principal oppresseur des femmes. Dans la plupart de ces œuvres, il est diffamé, culpabilisé et tenu responsable de la condition subalterne, opprimée et soumise des femmes. Ces écrivaines noires dénoncent le patriarcat comme un système perpétuant l’infériorisation et la marginalisation des femmes. Dans ce contexte, cet article soutient que le recueil de nouvelles, Ah ! Les femmes d’Isaïe Biton Koulibaly constitue une réponse aux récits féministes africains. Son objectif principal est de dédouaner l’homme de toute culpabilité tout en mettant en lumière les défauts des femmes, aussi bien dans la sphère conjugale qu’au-delà. En se focalisant sur le patriarcat comme réflexion de base, nous démontrons que les nouvelles dans Ah ! Les femmes … sont un prétexte pour plaider le retour du patriarcat. L’auteur semble illustrer, à travers ses nouvelles, que les femmes africaines portent des défauts irrémédiables et par la suite, ne méritent pas les privilèges dont elles jouissent en Afrique contemporaine. A travers l’œuvre de l’auteur, il apparait clairement une volonté de restaurer l’idéologie patriarcale rétrograde, un système vigoureusement combattu par les activistes féministes africaines dans leurs écrits. Il est conclu que les écrivains, hommes comme femmes, devraient privilégier la promotion de la complémentarité des genres dans leurs œuvres plutôt que d’adopter des positions partisanes
The impact of glucocorticoids on bone health and growth: endocrine and non-endocrine effects in children and young patients
No full text: Glucocorticoids have numerous applications in short and/or long-term therapy both in pediatric and young adults, based on their significant anti-inflammatory and immunosuppressive effects. Different routes of administration can be provided including topical, inhalatory and oral. Topical treatments are the first choice for many dermatologic conditions. The inhalatory form is widely used in asthma management while systemic pathologies often require oral administration. The risks for adverse effects are related to the dose and duration of therapy as well as the specific agent used. Therefore, long-term treatment has a negative impact on different metabolic systems and can lead to hypertension, dyslipidemia and insulin resistance. In particular, many studies emphasize the direct and indirect effects of glucocorticoids on bone health. Glucocorticoids are the most common iatrogenic cause of osteoporosis and can alter bone development in young adults. These side effects are due to an early and transient increase in bone resorption and a decrease in bone formation. Glucocorticoid-induced changes can act on the bone multicellular unit, bone cells and intracellular signaling pathways. Chronic use can also modify bone mass though indirect endocrine and non-endocrine effects by reducing the anabolic function of sex steroids and GH/IGF-1 axis, interfere with calcium metabolism, as well as muscle atrophy and central fat accumulation. The aim of our review is to revise the available evidence on the impact of glucocorticoid treatment on bone health related to endocrine and non-endocrine effects in young patients
MRS of Brain Metabolite Levels Demonstrates the Ability of Scavenging of Excess Brain Glutamate to Protect against Nerve Agent Induced Seizures
No full textThis study describes the use of in vivo magnetic resonance spectrocopy (MRS) to monitor brain glutamate and lactate levels in a paraoxon (PO) intoxication model. Our results show that the administration of recombinant glutamate-oxaloacetate transaminase (rGOT) in combination with oxaloacetate (OxAc) significantly reduces the brain-accumulated levels of glutamate. Previously we have shown that the treatment causes a rapid decrease of blood glutamate levels and creates a gradient between the brain and blood glutamate levels which leads to the efflux of excess brain glutamate into the blood stream thereby reducing its potential to cause neurological damage. The fact that this treatment significantly decreased the brain glutamate and lactate levels following PO intoxication suggests that it could become a new effective neuroprotective agent
Diffusion MRI and Q-Space Diffusion MRI: From Cerebral Ischemia to Multiple Sclerosis and Beyond
No full textStructural changes in glutamate cell swelling followed by multiparametric q-space diffusion MR of excised rat spinal cord
No full textDiffusion in the extracellular and intracellular spaces (ECS and ICS, respectively) was evaluated in excised spinal cords, before and after cell swelling induced by glutamate, by high b-value q-space diffusion MR of specific markers and water. The signal decays of deuterated tetramethylammonium (TMA-d12) chloride, an exogenous marker of the ECS, and N-acetyl aspartate (NAA), an endogenous marker of the ICS, were found to be non-mono-exponential at all diffusion times. The signal decays of these markers were found to depend on the diffusion time and the cell swelling induced by the glutamate. It was found, for example, that the mean displacements of the apparent fast and slow diffusion components of TMA-d12 are 7.21 ± 0.11 and 1.16 ± 0.05 μm, respectively at a diffusion time of 496 ms. After exposure of the spinal cords to 10 mM of glutamate, these values decreased to 6.62 ± 0.13 and 1.01 ± 0.05 μm, respectively. The mean displacement of NAA, however, showed a less pronounced opposite trend and increased after cell swelling induced by exposure to glutamate. q-Space diffusion MR of water was found to be sensitive to exposure to glutamate, and q-space diffusion MRI showed that a more pronounced decrease in the apparent diffusion coefficient and the mean displacement of water is observed in the gray matter (GM) of the spinal cord. All these changes demonstrate that diffusion MR is indeed sensitive to structural changes caused by cell swelling induced by glutamate. Multiparametric high b-value q-space diffusion MR is useful for obtaining microstructural information in neuronal tissues
Cerebellar learning properties are modulated by the CRF receptor in granular cells
No full textCorticotropin-releasing factor (CRF) and its type 1 receptor (CRFR1) play an important role in the responses to stressful challenges. Despite the well-established expression of CRFR1 in granular cells (GrCs), its role in procedural motor performance and memory formation remains elusive. To investigate the role of CRFR1 expression in cerebellar GrCs, we used a mouse model depleted of CRFR1 in these cells. We detected changes in the cellular learning mechanisms in GrCs depleted of CRFR1 in that they showed changes in intrinsic excitability and long-term synaptic plasticity. Moreover, male mice depleted of CRFR1 specifically in GrCs showed accelerated Pavlovian associative eye-blink conditioning, but no differences in baseline motor performance, locomotion or fear and anxiety-related behaviors. Last, we analyzed cerebella transcriptome of KO and control mice and detected prominent alterations in the expression of calcium signaling pathways components. Our findings shed light on the interplay between stress-related central mechanisms and cerebellar motor conditioning, highlighting the role of the CRF system in regulating particular forms of cerebellar learning.SIGNIFICANCE STATEMENTAlthough it is known that CRFR1 is highly expressed in the cerebellum, little attention has been given to its role in cerebellar functions in the behaving animal. Moreover, most of the attention was directed to the effect of CRF on Purkinje cells at the cellular level, and to this date, almost no data exist on the role of this stress-related receptor in other cerebellar structures. Here, we explored the behavioral and cellular effect of GrCs specific ablation of CRFR1 We found a profound effect on learning, both at the cellular and behavioral levels, without affecting baseline motor skills
Induction of Nitric-Oxide Metabolism in Enterocytes Alleviates Colitis and Inflammation-Associated Colon Cancer
No full textNitric oxide (NO) plays an established role in numerous physiological and pathological processes, but the specific cellular sources of NO in disease pathogenesis remain unclear, preventing the implementation of NO-related therapy. Argininosuccinate lyase (ASL) is the only enzyme able to produce arginine, the substrate for NO generation by nitric oxide synthase (NOS) isoforms. Here, we generated cell-specific conditional ASL knockout mice in combination with genetic and chemical colitis models. We demonstrate that NO derived from enterocytes alleviates colitis by decreasing macrophage infiltration and tissue damage, whereas immune cell-derived NO is associated with macrophage activation, resulting in increased severity of inflammation. We find that induction of endogenous NO production by enterocytes with supplements that upregulate ASL expression and complement its substrates results in improved epithelial integrity and alleviation of colitis and of inflammation-associated colon cance
