17 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
Antibody-Free Labeling of Malaria-Derived Extracellular Vesicles Using Flow Cytometry
No full textExtracellular vesicles (EVs) are cell-derived membrane-bound structures that are believed to play a major role in intercellular communication by allowing cells to exchange proteins and genetic cargo between them. In particular, pathogens, such as the malaria parasite Plasmodium (P.) falciparum, utilize EVs to promote their growth and to alter their host’s response. Thus, better characterization of these secreted organelles will enhance our understanding of the cellular processes that govern EVs’ biology and pathological functions. Here we present a method that utilizes a high-end flow cytometer system to characterize small EVs, i.e., with a diameter less than 200 nm. Using this method, we could evaluate different parasite-derived EV populations according to their distinct cargo by using antibody-free labeling. It further allows to closely monitor a sub-population of vesicles carrying parasitic DNA cargo. This ability paves the way to conducting a more ‘educated’ analysis of the various EV cargo components
La Influencia del ambiente filosófico en el arte de la Grecia Clásica (s. VI y V a C.)
No full textThis article analyzes the influence of the philosophical environment on the development of classical Greek art, focusing on sculpture from the 6th and 5th centuries BCE. Starting from the question of how ideas and philosophy affect artistic creation, it examines the transition from mythological and naturalistic thought to rationalism, as reflected in the aesthetic and technical evolution of sculpture. Through a comparison between “The Brothers Cleobis and Biton” by Polymedes of Argos and “The Discobolus” by Myron, the article highlights the shift from Egyptian rigidity to naturalistic movement as a manifestation of spirit and philosophical thought. The analysis draws on the contributions of Hegel, Plato, and Maritain, who argue that art is an expression of intellect and cultural context. It concludes that classical Greek sculpture is a privileged testimony to the interaction between philosophy, culture, and creativity, and that the artwork serves as a vehicle for truth and beauty, always referring to its author and its era.El presente trabajo buscó vislumbrar la influencia del ambiente filosófico en el desarrollo del arte griego clásico, centrándose en la escultura de los siglos VI y V a.C. A partir de la pregunta sobre cómo las ideas y la filosofía inciden en la creación artística, se examinó la transición desde el pensamiento mitológico y naturalista hacia el racionalismo, reflejada en la evolución estética y técnica de la escultura. Mediante la comparación entre “Los hermanos Cleobis y Biton” de Polímedes y “El discóbolo” de Mirón, se evidenció el paso de la rigidez del primer estilo griego (influencia egipcia) al movimiento naturalista posterior, como manifestación del pensamiento filosófico. El análisis se apoyó en Hegel, Platón y Maritain. Se concluyó que la escultura griega clásica constituye un testimonio de la interacción entre filosofía, cultura y creatividad, y que la obra de arte es vehículo de verdad y belleza, remitiendo siempre a su autor
Reassessment of the role of TSC, mTORC1 and microRNAs in amino acids-meditated translational control of TOP mRNAs.
No full textTOP mRNAs encode components of the translational apparatus, and repression of their translation comprises one mechanism, by which cells encountering amino acid deprivation downregulate the biosynthesis of the protein synthesis machinery. This mode of regulation involves TSC as knockout of TSC1 or TSC2 rescued TOP mRNAs translation in amino acid-starved cells. The involvement of mTOR in translational control of TOP mRNAs is demonstrated by the ability of constitutively active mTOR to relieve the translational repression of TOP mRNA upon amino acid deprivation. Consistently, knockdown of this kinase as well as its inhibition by pharmacological means blocked amino acid-induced translational activation of these mRNAs. The signaling of amino acids to TOP mRNAs involves RagB, as overexpression of active RagB derepressed the translation of these mRNAs in amino acid-starved cells. Nonetheless, knockdown of raptor or rictor failed to suppress translational activation of TOP mRNAs by amino acids, suggesting that mTORC1 or mTORC2 plays a minor, if any, role in this mode of regulation. Finally, miR10a has previously been suggested to positively regulate the translation of TOP mRNAs. However, we show here that titration of this microRNA failed to downregulate the basal translation efficiency of TOP mRNAs. Moreover, Drosha knockdown or Dicer knockout, which carries out the first and second processing steps in microRNAs biosynthesis, respectively, failed to block the translational activation of TOP mRNAs by amino acid or serum stimulation. Evidently, these results are questioning the positive role of microRNAs in this mode of regulation
Treatment of idiopathic generalized epilepsy - A review of the evidence
No full textIntroduction: Epilepsy is stratified into idiopathic partial, symptomatic partial, idiopathic generalized (IGE) and symptomatic generalized epilepsies. Areas covered: The epidemiology and clinical characteristics of IGE are reviewed in this paper. Clinically, IGE is characterized by the occurrence of any of the following three seizure types: absence seizures, myoclonic seizures and primarily generalized tonic-clonic seizures. To assess the presence of evidence-based data on the treatment of IGE, the literature was extensively reviewed for studies evaluating the treatment of IGE with various antiepileptic drugs. These studies were stratified into four classes based on recently described criteria. Class I studies were considered as providing evidence of the efficacy of the drug in patients with IGE. Finally, suggestions to evaluate the efficacy of a study drug in patients with IGE are presented. Expert opinion: Based on the reviewed data, there is strong evidence-based data to support the use of valproate and ethosuximide for the treatment of childhood absence seizures; for the use of topiramate as monotherapy or adjunctive therapy for patients with primarily generalized tonic-clonic seizures; for the use of adjunctive therapy with lamotrigine for the treatment of primarily generalized tonic-clonic seizures; and for the use of levetiracetam as adjunctive therapy for the treatment of myoclonic or primarily generalized tonic-clonic seizures. 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The kinase activity of mTOR is essential for translational control of TOP mRNAs.
No full text<p>(A) HEK293 cells were transfected with vectors expressing mTOR-wt, mTOR-rr or mTOR-rr-kd, two days later the cells were amino acid-starved for 3 h followed by 3 h refeeding without or with 20 nM rapamycin. Cytoplasmic proteins derived from the cells were subjected to Western blot analysis with the indicated antibodies. B) Cytoplasmic extracts derived from cells treated as described in (A), were subjected to polysomal analysis. C) HEK293 cells were amino acid-starved for 3 h, or amino acid-starved for 3 h followed by 3 h refeeding without or with 50 nM Torin1. Cytoplasmic proteins derived from the cells were subjected to Western blot analysis with the indicated antibodies. D) Cytoplasmic extracts derived from cells treated as described in (C) were subjected to polysomal analysis and the percentage of mRNA in polysomes is presented as an average ± SEM of three experiments.</p
Overexpression of RagB<sup>GTP</sup> can derepress TOP mRNA translation in amino acid-starved cells, but not in cells deprived of oxygen.
No full text<p>(A) HEK293 cells were infected with lentiviral expression vectors encoding FLAG-RagB or FLAG-RagB<sup>GTP</sup>. 48 h post infection cells were subjected to selection by puromycin and 48 h later were either kept untreated (+), amino acid-starved for 8 h (−AA), amino acid starved during the last 3 h of 24 h serum starvation (–Ser/AA) or deprived of oxygen (−O<sub>2</sub>) for 16 h. Cells were harvested and their cytoplasmic proteins were subjected to Western blot analysis using the indicated antibodies. (B) Polysomal analysis of cytoplasmic extracts from cells treated as describe in (A).</p
