Relating Fragile States to Social and Human Fragilities

Fragile States is a way of naming this particular category of states that have weak performance, insufficient service delivery, weak administrative and government power, and lack of legal rules. Little consideration is usually made to the fact that their own societies may also be fragile and easily jeopardised by inappropriate economic measures or external events. Poverty traps and social exclusion, unjust inequalities with lack of equity, feelings of insecurity and vulnerability, usually undermine the social fabric. Moreover, the people bear their own internal fragilities, which are based on the lack of capabilities and recognition, and interfere in the relationships between the groups that constitute the society. Therefore, dealing with the issue of fragility requires to consider various decision levels, from the personal one to the State level. Such an approach could allow fragile states to conceive preventive policies that would avoid the surge of a political crisis resulting from the combination of social conflict and individual failure.La notion d’Etats fragiles permet de caractériser des pays dont le pouvoir de gouvernement est faible, le cadre juridique et légal insuffisant, l’administration peu efficace et, en conséquence, la délivrance de services publics insuffisante. Mais elle prend peu en compte le fait que leurs propres sociétés peuvent aussi être fragiles et facilement détruites par des mesures economiques inappropriées ou par des événements extérieurs. Ainsi, les trappes à pauvreté, les structures d’inégalité pérennes, l’absence d’équité, de même que l’exclusion sociale, le sentiment d’insécurité et de vulnérabilité, ont tous pour effet de miner la cohésion sociale. De plus, les gens eux-mêmes, au sein d’une société donnée, portent aussi leur propres fragilités internes, basées sur un manque de capabilité et de reconnaissance, et ceci interfère dans les relations sociales. Si bien que si l’on veut aborder le problème de la fragilité dans toute sa dimension, il faut alors prendre en compte l’articulation des différents niveaux d’analyse où cette fragilité se déploie, du niveau personnel au niveau propre à l’Etat. L’intérêt d’une telle démarche est qu’elle permet aux Etats fragiles de concevoir des mesures de politique préventives qui leur permettraient d’éviter l’apparition de crises politiques graves, comme conséquence de la combinaison de situations sociales conflictuelles et d’échecs individualisés

Encephalopathy induced by Alzheimer brain inoculation in a non-human primate.

Alzheimer's disease is characterized by cognitive alterations, cerebral atrophy and neuropathological lesions including neuronal loss, accumulation of misfolded and aggregated β-amyloid peptides (Aβ) and tau proteins. Iatrogenic induction of Aβ is suspected in patients exposed to pituitary-derived hormones, dural grafts, or surgical instruments, presumably contaminated with Aβ. Induction of Aβ and tau lesions has been demonstrated in transgenic mice after contamination with Alzheimer's disease brain homogenates, with very limited functional consequences. Unlike rodents, primates naturally express Aβ or tau under normal conditions and attempts to transmit Alzheimer pathology to primates have been made for decades. However, none of earlier studies performed any detailed functional assessments. For the first time we demonstrate long term memory and learning impairments in a non-human primate (Microcebus murinus) following intracerebral injections with Alzheimer human brain extracts. Animals inoculated with Alzheimer brain homogenates displayed progressive cognitive impairments (clinical tests assessing cognitive and motor functions), modifications of neuronal activity (detected by electroencephalography), widespread and progressive cerebral atrophy (in vivo MRI assessing cerebral volume loss using automated voxel-based analysis), neuronal loss in the hippocampus and entorhinal cortex (post mortem stereology). They displayed parenchymal and vascular Aβ depositions and tau lesions for some of them, in regions close to the inoculation sites. Although these lesions were sparse, they were never detected in control animals. Tau-positive animals had the lowest performances in a memory task and displayed the greatest neuronal loss. Our study is timely and important as it is the first one to highlight neuronal and clinical dysfunction following inoculation of Alzheimer's disease brain homogenates in a primate. Clinical signs in a chronic disease such as Alzheimer take a long time to be detectable. Documentation of clinical deterioration and/or dysfunction following intracerebral inoculations with Alzheimer human brain extracts could lead to important new insights about Alzheimer initiation processes

Co-lethality studied as an asset against viral drug escape: the HIV protease case

International audienceBackground: Co-lethality, or synthetic lethality is the documented genetic situation where two, separately non-lethal mutations, become lethal when combined in one genome. Each mutation is called a "synthetic lethal" (SL) or a co-lethal. Like invariant positions, SL sets (SL linked couples) are choice targets for drug design against fast-escaping RNA viruses: mutational viral escape by loss of affinity to the drug may induce (synthetic) lethality.Results: From an amino acid sequence alignment of the HIV protease, we detected the potential SL couples, potential SL sets, and invariant positions. From the 3D structure of the same protein we focused on the ones that were close to each other and accessible on the protein surface, to possibly bind putative drugs. We aligned 24,155 HIV protease amino acid sequences and identified 290 potential SL couples and 25 invariant positions. After applying the distance and accessibility filter, three candidate drug design targets of respectively 7 (under the flap), 4 (in the cantilever) and 5 (in the fulcrum) amino acid positions were found.Conclusions: These three replication-critical targets, located outside of the active site, are key to our anti-escape strategy. Indeed, biological evidence shows that 2/3 of those target positions perform essential biological functions. Their mutational variations to escape antiviral medication could be lethal, thus limiting the apparition of drug-resistant strains

Embedding Emotions Within Automatically Generated Brand Names

International audienceBrand names are everywhere and are more and more important due to the rate which new products are issued at. For instance, the French institute INPI (Institut National de la Propriété Industrielle) in charge of name registration collects more than two millions of new names every year. Names have been recognized to embed many characteristics of the products or company they are related to. For instance, a name like "discipline" can invoke feelings like "unhappiness". However, they have not been extensively studied, neither from the point of view of cognitive science/linguistics nor from the computer science point of view. For this reason, the automatic generation of brand names is a very difficult task, which has not been given much attention yet. In this paper, we thus propose a new method to automatically embed emotions within brand names

Fouille de données issues d'études psychologiques liées au vieillissement : extraction de règles graduelles

International audienceAlzheimer disease impacts memory and reduces cognitive functions and social relationships, interactions, self-decision making and autonomy. In this paper, we describe how data mining tools can help psychologists to analyze the data they collect. This work is the result of a collaboration between psychologists and computer scientists. It aims at developing methods and tools to handle the data collected by psychologists to extract relevant knowledge.La mémoire humaine n'est pas un simple réceptacle du passé. Elle permet de comprendre le présent et de se projeter dans l'avenir. Elle est l'identité même de l'être. Les patients atteints de la maladie d'Alzheimer souffrent de pertes de mémoire qui réduisent leurs fonctions cognitives et donc leurs relations sociales, leurs interactions, leurs capacités à décider par eux mêmes, et finalement leur autonomie. Cet article est issu d'une collaboration entre une équipe de psychologues, spécialistes de la mémoire et de la maladie d'Alzheimer et une équipe d'informaticiens, spécialistes de la fouille de données. Cette collaboration vise à développer des méthodes et des outils de fouille adaptés aux données issues d'études psychologiques en vue d'en extraire des connaissances nouvelles

Molecular Characterization of a Rare Case of Monozygotic Dichorionic Diamniotic Twin Pregnancy after Single Blastocyst Transfer in Preimplantation Genetic Testing (PGT)

International audiencePreimplantation genetic testing (PGT) is widely used to select unaffected embryos, increasing the odds of having a healthy baby. During the last few decades, it was accepted that monozygotic dichorionic diamniotic twin pregnancies occurred from the embryo splitting before Day 3 postfertilization according to Corner’s dogma. Hence, the occurrence of a dichorionic diamniotic twin pregnancy after a single blastocyst transfer was considered a dizygotic pregnancy resulting from blastocyst transfer and concurrent natural fertilization. In our study, we have provided for the first time molecular proof that a single blastocyst transfer can result in a monozygotic dichorionic diamniotic twin pregnancy, invalidating Corner’s dogma. In this case, we recommend systematically assessing the genetic status of dichorionic twins after single blastocyst transfer using prenatal diagnosis to exclude the risk from a potential concurrent spontaneous pregnancy and to ensure that both fetuses are unaffected. To achieve this goal, we have developed here an innovative noninvasive prenatal diagnosis by exclusion of paternal variants with droplet digital PCR, maximizing the reliability of genetic diagnosis. Further multicentric prospective studies using genetic testing are now required to establish the rate of blastocyst splitting leading to dichorionic pregnancy in PGT and to identify the risk factors

A dual role of adenosine A2A receptors in 3-nitropropionic acid-induced striatal lesions: implications for the neuroprotective potential of A2A antagonists.

Reduction of A2A receptor expression is one of the earliest events occurring in both Huntington's disease (HD) patients and mice overexpressing the N-terminal part of mutated huntingtin. Interestingly, increased activity of A2A receptors has been found in striatal cells prone to degenerate in experimental models of this neurodegenerative disease. However, the role of A2A receptors in the pathogenesis of HD remains obscure. In the present study, using A2A-/- mice and pharmacological compounds in rat, we demonstrate that striatal neurodegeneration induced by the mitochondrial toxin 3-nitropropionic acid (3NP) is regulated by A2A receptors. Our results show that the striatal outcome induced by 3NP depends on a balance between the deleterious activity of presynaptic A2A receptors and the protective activity of postsynaptic A2A receptors. Moreover, microdialysis data demonstrate that this balance is anatomically determined, because the A2A presynaptic control on striatal glutamate release is absent within the posterior striatum. Therefore, because blockade of A2A receptors has differential effects on striatal cell death in vivo depending on its ability to modulate presynaptic over postsynaptic receptor activity, therapeutic use of A2A antagonists in Huntington's as well as in other neurodegenerative diseases could exhibit undesirable biphasic neuroprotective-neurotoxic effects.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

THY-Tau22 mouse model accumulates more tauopathy at late stage of the disease in response to microglia deactivation through TREM2 deficiency

International audienceThe role played by microglia has taken the center of the stage in the etiology of Alzheimer's disease (AD). Several genome-wide association studies carried out on large cohorts of patients have indeed revealed a large number of genetic susceptibility factors corresponding to genes involved in neuroinflammation and expressed specifically by microglia in the brain. Among these genes TREM2, a cell surface receptor expressed by microglia, arouses strong interest because its R47H variant confers a risk of developing AD comparable to the ε4 allele of the APOE gene. Since this discovery, a growing number of studies have therefore examined the role played by TREM2 in the evolution of amyloid plaques and neurofibrillary tangles, the two brain lesions characteristic of AD. Many studies report conflicting results, reflecting the complex nature of microglial activation in AD. Here, we investigated the impact of TREM2 deficiency in the THY-Tau22 transgenic line, a well-characterized model of tauopathy. Our study reports an increase in the severity of tauopathy lesions in mice deficient in TREM2 occurring at an advanced stage of the pathology. This exacerbation of pathology was associated with a reduction in microglial activation indicated by typical morphological features and altered expression of specific markers. However, it was not accompanied by any further changes in memory performance. Our longitudinal study confirms that a defect in microglial TREM2 signaling leads to an increase in neuronal tauopathy occurring only at late stages of the disease

Complex roles for reactive astrocytes in the triple transgenic mouse model of Alzheimer disease

In Alzheimer disease (AD), astrocytes undergo complex changes and become reactive. Theconsequences of this reaction are still unclear. To evaluate the net impact of reactive astrocytes in AD,we recently developed viral vectors targeting astrocytes that either activate or inhibit the JAK2-STAT3 pathway, a central cascade controlling astrocyte reaction.We aimed to evaluate whether reactive astrocytes contribute to Tau as well as amyloid pathologies inthe hippocampus of 3xTg-AD mice, an AD model that develops Tau hyperphosphorylation andaggregation in addition to amyloid deposition. JAK2-STAT3 pathway-mediated modulation ofreactive astrocytes in the hippocampus of 3xTg-AD mice, did not significantly influence Tauphosphorylation or amyloid processing and deposition, at early, advanced and terminal stage of thedisease. Interestingly, inhibition of the JAK2-STAT3 pathway in hippocampal astrocytes did notimprove short-term spatial memory in the Y maze but it reduced anxiety in the elevated plus maze.Our unique approach to specifically manipulate reactive astrocytes in situ show these cells may impactbehavioral outcomes without influencing Tau or amyloid pathology

Dopamine Gene Therapy for Parkinson’s Disease in a Nonhuman Primate Without Associated Dyskinesia

International audienceA gene therapy approach for the treatment of Parkinson’s disease