Les sites fragiles autosomiques. [[Autosomal fragile sites].

It is possible to distribute the 17 autosomic fragile sites presently known in three categories according to their sensitivity: BrdU-sensitive sites (10q25, 16q22, 17p12), distamycin A-sensitive sites (16q22, 17p12) and folate- and thymidilate-sensitive sites (2q11-q14, 3p14, 6p23, 7p11, 8q22, 9p21, 9q32, 10q23, 11q13, 11q23, 12q13, 16p12, 16q23, 17p12, 20p11). Four fundamental problems are discussed, first the relation between the presence of a fragile site and the phenotype, secondly the incidence of autosomic sites, third the origin of fragility (particularity of DNA structure, defect of the DNA/proteins binding and abnormal arrangement of chromatin, abnormality of the metaphasic scaffold) and fourth the localization of fragile sites.

Translating molecular advances in fragile X syndrome into therapy: a review.

Fragile X syndrome is an inherited disease with cognitive, behavioral, and neurologic manifestations, resulting from a single genetic mutation. A variety of treatments that target individual symptoms of fragile X syndrome are currently utilized with limited efficacy. Research in animal models has resulted in the development of potential novel pharmacologic treatments that target the underlying molecular defect in fragile X syndrome, rather than the resultant symptoms. This review describes recent advances in our understanding of the molecular basis of fragile X syndrome and summarizes the ongoing clinical research programs.

A novel semi-fragile forensic watermarking scheme for remote sensing images

Peer-reviewed

Fragile X-syndrome: literature review and report of two cases

Fragile X-syndrome is caused by a mutation in chromosome X. It is one of the most frequent causes of learning disability. The most frequent manifestations of fragile X-syndrome are learning disability, different orofacial morphological alterations and an increase in testicle size. The disease is associated with cardiac malformations, joint hyperextension and behavioural alterations. We present two male patients aged 17 and 10 years, treated in our Service due to severe gingivitis. Both showed the typical facial and dental characteristics of the syndrome. In addition, we detected the presence of root anomalies such as taurodontism and root bifurcation, which had not been associated with fragile X-syndrome in the literature. In some cases these root malformations have been associated with other sex-linked congenital syndromes, though in none of the studies published in the literature have they been related with fragile X-syndrome. This syndrome is relevant due to its high prevalence, the presentation of certain oral and facial characteristics that can facilitate the diagnosis, and the few cases published to date

Dysregulated ADAM10-Mediated Processing of APP during a Critical Time Window Leads to Synaptic Deficits in Fragile X Syndrome.

The Fragile X mental retardation protein (FMRP) regulates neuronal RNA metabolism, and its absence or mutations leads to the Fragile X syndrome (FXS). The β-amyloid precursor protein (APP) is involved in Alzheimer's disease, plays a role in synapse formation, and is upregulated in intellectual disabilities. Here, we show that during mouse synaptogenesis and in human FXS fibroblasts, a dual dysregulation of APP and the α-secretase ADAM10 leads to the production of an excess of soluble APPα (sAPPα). In FXS, sAPPα signals through the metabotropic receptor that, activating the MAP kinase pathway, leads to synaptic and behavioral deficits. Modulation of ADAM10 activity in FXS reduces sAPPα levels, restoring translational control, synaptic morphology, and behavioral plasticity. Thus, proper control of ADAM10-mediated APP processing during a specific developmental postnatal stage is crucial for healthy spine formation and function(s). Downregulation of ADAM10 activity at synapses may be an effective strategy for ameliorating FXS phenotypes.

Les anticoagulants oraux directs en 2015 chez le patient âgé: focus chez le sujet fragile

Depuis les études princeps de phase III de non-inf ériorité comparant les anticoagulants oraux directs (AOD) à la warfarine, de nombreuses études ont essayé de répondre à la question de l'efficacité et de la sécurité d'utilisation des AOD chez les patients âgés. Ces études sont des études de sous-groupes complémentaires issues des études princeps ou des études de pharmacovigilance en postmarketing utilisant des données médicoéconomiques à grande échelle. De nombreux biais, par définition, peuvent entraîner une distorsion des résultats dans de telles études, rendant leur interprétation prudente. Aucun essai randomisé contrôlé n'a à ce jour comparé les AOD à la warfarine chez des patients de 80 ans ou plus et a fortiori chez des sujets âgés fragiles. En pratique, chez le patient âgé fragile, il n'y a pas de consensus quant au choix des anticoagulants à prescrire en cas de fibrillation atriale (FA) et de la maladie thromboembolique veineuse (MTEV). Quant au choix de l'AOD à privilégier chez le sujet âgé, faute d'études de comparaison directe disponibles à ce jour, il apparaît difficile de se prononcer. Toutefois, les données disponibles, tant sur le plan pharmacologique que celles issues des études complémentaires, semblent montrer que le dabigatran offre un profil bénéfice/risque moins favorable que les autres AOD. Néanmoins, les résultats prometteurs de l'idarucizumab, antidote du dabigatran, pourraient contribuer à améliorer ce rapport à l'avenir.

Experience with molecular and cytogenetic diagnosis of fragile X syndrome in Brazilian families

We report on the cytogenetic and DNA analysis of 55 families with the fragile X (FMR-1 locus) mutation (318 individuals and 15 chorionic villi samples). A total of 129 males were investigated, 54 mentally normal and 75 presenting mental retardation. Among the 54 normal males, 11 had the premutation, and none expressed the fragile site. The full mutation was detected in 73 retarded males, and 14 (18%) presented a premutation along with the full mutation (mosaics). All of them manifested the fragile site. The frequencies of fragile site expression correlated positively with the sizes of the expansion of the CGG repeats (D). Among 153 normal females, 85 were found to be heterozygous for the premutation and 15 had the full mutation. In the premutated females the fragile site was not observed or it occurred at frequencies that did not differ from those observed in 53 noncarriers. Cytogenetic analysis was thus ineffective for the diagnosis of premutated males or females. Among the 51 heterozygotes for the full mutation, 36 (70%) had some degree of mental impairment. As in males, a positive correlation was detected between the frequencies of fragile site manifestation and the size of the expansion. However, the cytogenetic test was less effective for the detection of fully mutated females, than in the case of males, since 14% false negative results were found among females. Segregation analysis confirmed that the risk of mental retardation in the offspring of heterozygotes increases with the length of D. The average observed frequency of mental retardation in the offspring of all heterozygotes was 30%. There was no indication of meiotic drive occurring in female carriers, since the number of individuals who inherited the mutation did not differ from the number of those inheriting the normal allele. No new mutations were detected in the 55 genealogies studied here.

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.

L'emploi et la citoyenneté : une fragile alliance. Étude du lien entre l'emploi et la citoyenneté

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Archéologie amérindienne au Québec : intérêts divergents et collaboration fragile entre archéologues et communautés autochtones

Étude de cas / Case study

Auditory and visual event-related potential alterations in fragile X syndrome

Le syndrome du X fragile (SXF) est la première cause héréditaire de déficience intellectuelle et également la première cause monogénique d’autisme. Le SXF est causé par l'expansion de la répétition du nucléotide CGG sur le gène FMR1, ce qui empêche l’expression de la protéine FMRP. L’absence du FMRP mène à une altération du développement structurel et fonctionnel de la synapse, ce qui empêche la maturation des synapses induite par l’activité et l’élagage synaptique, qui sont essentiels pour le développement cérébral et cognitif. Nous avons investigué les potentiels reliés aux événements (PRE) évoqués par des stimulations fondamentales auditives et visuelles dans douze adolescents et jeunes adultes (10-22) atteints du SXF, ainsi que des participants contrôles appariés en âge chronologique et développemental. Les résultats indiquent un profil des PRE altéré, notamment l’augmentation de l’amplitude de N1 auditive, par rapport aux deux groupes contrôle, ainsi que l’augmentation des amplitudes de P2 et N2 auditifs et de la latence de N2 auditif. Chez les patients SXF, le traitement sensoriel semble être davantage perturbé qu’immature. En outre, la modalité auditive semble être plus perturbée que la modalité visuelle. En combinaison avec des résultats anatomique du cerveau, des mécanismes biochimiques et du comportement, nos résultats suggèrent une hyperexcitabilité du système nerveux dans le SXF.

Fragile-glass behavior of a short-range p-spin model

We propose a short-range generalization of the p-spin interaction spin-glass model. The model is well suited to test the idea that an entropy collapse is at the bottom line of the dynamical singularity encountered in structural glasses. The model is studied in three dimensions through Monte Carlo simulations, which put in evidence fragile glass behavior with stretched exponential relaxation and super-Arrhenius behavior of the relaxation time. Our data are in favor of a Vogel-Fulcher behavior of the relaxation time, related to an entropy collapse at the Kauzmann temperature. We, however, encounter difficulties analogous to those found in experimental systems when extrapolating thermodynamical data at low temperatures. We study the spin-glass susceptibility, investigating the behavior of the correlation length in the system. We find that the increase of the relaxation time is accompanied by a very slow growth of the correlation length. We discuss the scaling properties of off-equilibrium dynamics in the glassy regime, finding qualitative agreement with the mean-field theory.

Evaluation of noise levels experienced by medically fragile neonates during emergency helicopter transport

There was a concern medically fragile infants may be exposed to high noise levels during emergency helicopter transport. This study had been initiated in 2007. Data was collected using a Larson Davis noise dosimeter. The purpose of this study was to collect additional data to evaluate the noise exposure experienced by medically fragile neonates during emergency transport via helicopter inbound/outbound of St. Louis Children’s Hospital, St. Louis, MO. The results suggested neonates may be exposed to noise levels ranging 85 to 95 dBA during transport. These high noise exposures may pose a risk to hearing.