Царський і республіканський Рим в антикознавчих дослідженнях М.П. Драгоманова

У статті розглянуто особливості вивчення та рецепції римської історії VIII–I ст. до н. е. в антикознавчих студіях М. Драгоманова. Зроблено висновок, що дослідження М. Драгоманова з історії Риму вплинули на формування наукових і суспільно-політичних поглядів вченого, а також Лесі Українки та І. Франка.In the article peculiarities of study and reception of Roman history VIII–I centuries B.C. in M. Drahomanov’s classical researches are highlighted. The author concludes that M. Drahomanov’s Roman classical studies influenced on formation of scientific and political views of M. Drahomanov, Lesya Ukrainka, I. Franko

Chronic Treatment with a Promnesiant GABA-A α5-Selective Inverse Agonist Increases Immediate Early Genes Expression during Memory Processing in Mice and Rectifies Their Expression Levels in a Down Syndrome Mouse Model

Decrease of GABAergic transmission has been proposed to improve memory functions. Indeed, inverse agonists selective for α5 GABA-A-benzodiazepine receptors (α5IA) have promnesiant activity. Interestingly, we have recently shown that α5IA can rescue cognitive deficits in Ts65Dn mice, a Down syndrome mouse model with altered GABAergic transmission. Here, we studied the impact of chronic treatment with α5IA on gene expression in the hippocampus of Ts65Dn and control euploid mice after being trained in the Morris water maze task. In euploid mice, chronic treatment with α5IA increased IEGs expression, particularly of c-Fos and Arc genes. In Ts65Dn mice, deficits of IEGs activation were completely rescued after treatment with α5IA. In addition, normalization of Sod1 overexpression in Ts65Dn mice after α5IA treatment was observed. IEG expression regulation after α5IA treatment following behavioral stimulation could be a contributing factor for both the general promnesiant activity of α5IA and its rescuing effect in Ts65Dn mice alongside signaling cascades that are critical for memory consolidation and cognition

Characterization of nanomedicines’ surface coverage using molecular probes and capillary electrophoresis

International audienceA faithful characterization of nanomedicine (NM) is needed for a better understanding of their in vivo outcomes. Size and surface charge are studied with well-established methods. However, other relevant parameters for the understanding of NM behavior in vivo remain largely inaccessible. For instance, the reactive surface of nanomedicines, which are often grafted with macromolecules to decrease their recognition by the immune system, is excluded from a systematic characterization. Yet, it is known that a subtle modification of NMs' surface characteristics (grafting density, molecular architecture and conformation of macromolecules) is at the root of major changes in the presence of biological components. In this work, a method that investigates the steric hindrance properties of the NMs’ surface coverage based on its capacity to exclude or allow adsorption of well-defined proteins was developed based on capillary electrophoresis. A series of proteins with different molecular weights (MW) were used as molecular probes to screen their adsorption behavior on nanoparticles bearing different molecular architectures at their surface. This novel strategy evaluating to some degree a functionality of NMs can bring additional information about their shell property and might allow for a better perception of their behavior in the presence of biological components. The developed method could discriminate nanoparticles with a high surface coverage excluding high MW proteins from nanoparticles with a low surface coverage that allowed high MW proteins to adsorb on their surface. The method has the potential for further standardization and automation for a routine use. It can be applied in quality control of NMs and to investigate interactions between proteins and NM in different situations

Intensity Control in GANIL's Experimental Rooms

TUPF31International audienceThe safety re-examination of existing GANIL facilities requires the implementation of a safety system which makes a control of the beam intensity sent to the experimental rooms possible. The aim is to demonstrate that beam intensities stay below the authorized limits defined by the safety GANIL group. The challenge is to be able to measure by a non-interceptive method a wide range of beam intensities from 5nA to 5 A with a maximum uncertainty of 5%, independently of the frequency (from 7 to 14.5MHz) and the beam energy (from 1.2 to 95MeV.A). After a comparative study, two types of high frequency diagnostics were selected, the capacitive pick-up and the fast current transformer. This paper presents the signal simulations from diagnostics with different beam energies, the uncertainty calculations and the results of the first tests with beam

Curve counting via stable pairs in the derived category

For a nonsingular projective 3-fold $X$, we define integer invariants virtually enumerating pairs $(C,D)$ where $C\subset X$ is an embedded curve and $D\subset C$ is a divisor. A virtual class is constructed on the associated moduli space by viewing a pair as an object in the derived category of $X$. The resulting invariants are conjecturally equivalent, after universal transformations, to both the Gromov-Witten and DT theories of $X$. For Calabi-Yau 3-folds, the latter equivalence should be viewed as a wall-crossing formula in the derived category. Several calculations of the new invariants are carried out. In the Fano case, the local contributions of nonsingular embedded curves are found. In the local toric Calabi-Yau case, a completely new form of the topological vertex is described. The virtual enumeration of pairs is closely related to the geometry underlying the BPS state counts of Gopakumar and Vafa. We prove that our integrality predictions for Gromov-Witten invariants agree with the BPS integrality. Conversely, the BPS geometry imposes strong conditions on the enumeration of pairs.Comment: Corrected typos and duality error in Proposition 4.6. 47 page

Contribution of the d-Serine-Dependent Pathway to the Cellular Mechanisms Underlying Cognitive Aging

An association between age-related memory impairments and changes in functional plasticity in the aging brain has been under intense study within the last decade. In this article, we show that an impaired activation of the strychnine-insensitive glycine site of N-methyl-d-aspartate receptors (NMDA-R) by its agonist d-serine contributes to deficits of synaptic plasticity in the hippocampus of memory-impaired aged rats. Supplementation with exogenous d-serine prevents the age-related deficits of isolated NMDA-R-dependent synaptic potentials as well as those of theta-burst-induced long-term potentiation and synaptic depotentiation. Endogenous levels of d-serine are reduced in the hippocampus with aging, that correlates with a weaker expression of serine racemase synthesizing the amino acid. On the contrary, the affinity of d-serine binding to NMDA-R is not affected by aging. These results point to a critical role for the d-serine-dependent pathway in the functional alterations of the brain underlying memory impairment and provide key information in the search for new therapeutic strategies for the treatment of memory deficits in the elderly

Association of plasma Aβ40/Aβ42 ratio and brain Aβ accumulation: testing a whole-brain PLS-VIP in individuals at risk of Alzheimer's disease

Molecular and brain regional/network-wise pathophysiological changes at preclinical stages of Alzheimer's disease (AD) have primarily been found through knowledge-based studies conducted in late-stage mild cognitive impairment/dementia populations. However, such an approach may compromise the objective of identifying the earliest spatial-temporal pathophysiological processes. We investigated 261 individuals with subjective memory complaints, a condition at increased risk of AD, to test a whole-brain, non-a-priori method based on partial least squares, in unraveling the association between plasma Aβ42/Aβ40 ratio and an extensive set of brain regions characterized through molecular imaging of Aβ accumulation and cortical metabolism. Significant associations were mapped onto large-scale networks, identified through an atlas and by knowledge, to elaborate on the reliability of the results. Plasma Aβ42/40 ratio was associated with Aβ-PET uptake (but not FDG-PET) in regions generally investigated in preclinical AD such as those belonging to the default mode network, but also in regions/networks normally not accounted - including the central executive and salience networks - which likely have a selective vulnerability to incipient Aβ accumulation. The present whole-brain approach is promising to investigate early pathophysiological changes of AD to fully capture the complexity of the disease, which is essential to develop timely screening, detection, diagnostic, and therapeutic interventions