Search results for "fragile"
showing 10 items of 40 documents
FANCD2 modulates the mitochondrial stress response to prevent common fragile site instability
2021
Common fragile sites (CFSs) are genomic regions frequently involved in cancer-associated rearrangements. Most CFSs lie within large genes, and their instability involves transcription- and replication-dependent mechanisms. Here, we uncover a role for the mitochondrial stress response pathway in the regulation of CFS stability in human cells. We show that FANCD2, a master regulator of CFS stability, dampens the activation of the mitochondrial stress response and prevents mitochondrial dysfunction. Genetic or pharmacological activation of mitochondrial stress signaling induces CFS gene expression and concomitant relocalization to CFSs of FANCD2. FANCD2 attenuates CFS gene transcription and pr…
Dicer prevents genome instability in response to replication stress
2019
Dicer, an endoribonuclease best-known for its role in microRNA biogenesis and RNA interference pathway, has been shown to play a role in the DNA damage response and repair of double-stranded DNA breaks (DSBs) in mammalian cells. However, it remains unknown whether Dicer is also important to preserve genome integrity upon replication stress. To address this question, we focused our study on common fragile sites (CFSs), which are susceptible to breakage after replication stress. We show that inhibition of the Dicer pathway leads to an increase in CFS expression upon induction of replication stress and to an accumulation of 53BP1 nuclear bodies, indicating transmission of replication-associate…
Dysregulated Prefrontal Cortex Inhibition in Prepubescent and Adolescent Fragile X Mouse Model
2020
Changes in excitation and inhibition are associated with the pathobiology of neurodevelopmental disorders of intellectual disability and autism and are widely described in Fragile X syndrome (FXS). In the prefrontal cortex (PFC), essential for cognitive processing, excitatory connectivity and plasticity are found altered in the FXS mouse model, however, little is known about the state of inhibition. To that end, we investigated GABAergic signaling in the Fragile X Mental Retardation 1 (FMR1) knock out (Fmr1-KO) mouse medial PFC (mPFC). We report changes at the molecular, and functional levels of inhibition at three (prepubescence) and six (adolescence) postnatal weeks. Functional changes we…
Neuroactive Steroids Reverse Tonic Inhibitory Deficits in Fragile X Syndrome Mouse Model
2018
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. A reduction in neuronal inhibition mediated by γ-aminobutyric acid type A receptors (GABAARs) has been implicated in the pathophysiology of FXS. Neuroactive steroids (NASs) are known allosteric modulators of GABAAR channel function, but recent studies from our laboratory have revealed that NASs also exert persistent metabotropic effects on the efficacy of tonic inhibition by increasing the protein kinase C (PKC)-mediated phosphorylation of the α4 and β3 subunits which increase the membrane expression and boosts tonic inhibition. We have assessed the GABAergic signaling in the hippocampus of fragile X ment…
Fragile-X carrier females: evidence for a distinct psychopathological phenotype?
1996
The present study examined 35 mothers (29 premutation carriers) of children with fragile-X syndrome in measures of intelligence and psychiatric disorders by comparing them with two control groups: a) 30 mothers of children in the general population and b) 17 mothers of non-fra-X retarded children with autism. Premutation carriers had a higher frequency of affective disorders than mothers from the general population. Preliminary data indicate that normally intelligent premutation carriers of the fra-X genetic abnormality have a similar frequency of affective disorders (DSM-III-R criteria [APA, 1987]) than mothers of autistic children. Neither carriers of the premutation nor carriers of the f…
Sleep phenotypes of intellectual disability: a polysomnographic evaluation in subjects with Down syndrome and Fragile X syndrome
2008
Abstract Objective To analyze sleep architecture and NREM sleep alterations by means of the Cyclic Alternating Pattern (CAP) in children with Down syndrome (DS) and Fragile-X syndrome (fraX), the two most common causes of inherited mental retardation, in order to find out eventual alterations of their sleep microstructure related to their mental retardation phenotypes. Methods Fourteen patients affected by fraX (mean age 13.1 years) and 9 affected by Down syndrome (mean age 13.8 years) and 26 age-matched normal controls were included. All subjects underwent overnight polysomnography in the sleep laboratory, after one adaptation night and their sleep architecture and CAP were visually scored…
A new pericentric inv(8) in acute nonlymphocytic leukemia.
1993
Abstract Chromosome studies were carried out on unstimulated bone marrow cells from a patient with a diagnosis of acute nonlymphocytic leukemia (FAB M6 ANLL). Cytogenetic analysis revealed a mosaic chromosome pattern 46,XX46,XX,inv(8)(p21q24). This pericentric inversion has not been previously described in ANLL. Because, fragile sites, zinc finger gene loci, and the MYC protooncogene have been localized to band 8q24, a putative role for these sites and genes could be considered.
The European Union’s Development Policy: A Balancing Act between ‘A More Comprehensive Approach’ and Creeping Securitization
2016
More than a decade after the release of the European Security Strategy (ESS) in 2003, its affirmation that development and security policy should work together is still one of its most discussed features. The vision of a more comprehensive — if not integrated — approach to security and development was underwritten by substantial changes to the EU’s external relations bureaucracy following the 2009 Lisbon Treaty. This ambition raises several important questions regarding the potential ‘securitization’ of EU development policy and foreign aid. Have security concerns had a growing influence on EU development policy and aid allocation? Do key concepts that have become prominent since the ESS wa…
Aid to education in fragile states: an unresolved issue
2013
En ligne sur : http://www.norrag.org/en/publications/norrag-news/online-version/education-and-development-in-the-post-2015-landscapes/detail/aid-to-education-in-fragile-states-an-unresolved-issue.html; The analysis of the situation of the fragile states in the last decade vis-à-vis official development assistance to education indicates a current contradiction between the inclusiveness of the EFA goals and the exclusionary nature of the paradigm of aid effectiveness. Today, financial instruments to support the development of education systems are seemingly not yet suited to situations of fragility
L'aide internationale en éducation dans les États fragiles : entre efficacité et justice
2013
En affirmant que l'aide internationale n'a aucun effet en matière de croissance dans les environnements politiques ou institutionnels défaillants, les travaux de Burnside et Dollar (1997), ont profondément influencé la réflexion sur l'allocation de l'aide. Les principes de sélectivité et d'allocation optimale de l'aide qui découlent de ces analyses ont en effet inspiré les réformes des politiques d'aide de nombreux bailleurs. Le message peut paraître séduisant : le ciblage des pays pauvres qui mettent en ouvre de bonnes politiques accroît l'efficacité de l'aide. Si pour certains la mobilisation autour des objectifs du millénaire pour le développement (OMD) a permis d'orienter davantage l'at…