15 research outputs found

    Inactive Atm abrogates DSB repair in mouse cerebellum more than does Atm loss, without causing a neurological phenotype

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    The genome instability syndrome, ataxia-telangiectasia (A-T) is caused by null mutations in the ATM gene, that lead to complete loss or inactivation of the gene's product, the ATM protein kinase. ATM is the primary mobilizer of the cellular response to DNA double-strand breaks (DSBs) – a broad signaling network in which many components are ATM targets. The major clinical feature of A-T is cerebellar atrophy, characterized by relentless loss of Purkinje and granule cells. In Atm-knockout (Atm-KO) mice, complete loss of Atm leads to a very mild neurological phenotype, suggesting that Atm loss is not sufficient to markedly abrogate cerebellar structure and function in this organism. Expression of inactive (“kinase-dead”) Atm (AtmKD) in mice leads to embryonic lethality, raising the question of whether conditional expression of AtmKD in the murine nervous system would lead to a more pronounced neurological phenotype than Atm loss. We generated two mouse strains in which AtmKD was conditionally expressed as the sole Atm species: one in the CNS and one specifically in Purkinje cells. Focusing our analysis on Purkinje cells, the dynamics of DSB readouts indicated that DSB repair was delayed longer in the presence of AtmKD compared to Atm loss. However, both strains exhibited normal life span and displayed no gross cerebellar histological abnormalities or significant neurological phenotype. We conclude that the presence of AtmKD is indeed more harmful to DSB repair than Atm loss, but the murine central nervous system can reasonably tolerate the extent of this DSB repair impairment. Greater pressure needs to be exerted on genome stability to obtain a mouse model that recapitulates the severe A-T neurological phenotype

    Activity changes in neuron-astrocyte networks in culture under the effect of norepinephrine.

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    The concerted activity of neuron-glia networks is responsible for the fascinating dynamics of brain functions. Although these networks have been extensively investigated using a variety of experimental (in vivo and in vitro) and theoretical models, the manner by which neuron-glia networks interact is not fully understood. In particular, how neuromodulators influence network-level signaling between neurons and astrocytes was poorly addressed. In this work, we investigated global effects of the neuromodulator norepinephrine (NE) on neuron-astrocyte network communication in co-cultures of neurons and astrocytes and in isolated astrocyte networks. Electrical stimulation was used to activate the neuron-astrocyte glutamate-mediated pathway. Our results showed dramatic changes in network activity under applied global perturbations. Under neuromodulation, there was a marked rise in calcium signaling in astrocytes, neuronal spontaneous activity was reduced, and the communication between neuron-astrocyte networks was perturbed. Moreover, in the presence of NE, we observed two astrocyte behaviors based on their coupling to neurons. There were also morphological changes in astrocytes upon application of NE, suggesting a physical cause underlies the change in signaling. Our results shed light on the role of NE in controlling sleep-wake cycles

    Another piece in the puzzle – A new PPNA site at Bir el-Maksur (Northern Israel)

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    Salvage excavations held at the site of Bir el-Maksur, Lower Galilee, revealed an extensive Pre-Pottery Neolithic A (PPNA) occupation alongside rich assemblages. Albeit the lack of clear architectural structures, the abundant fi nds demonstrate a wide variety of activities held at this locale, including faunal and floral resource processing and consumption, on-site lithic production and large-scale pyrotechnological activities. A complex secondary burial of two individuals accompanied with what might be interpreted as grave goods (mainly ground stones) indicates more complex, socio-cultural activities as well. As the Neolithic period represents an important departure from Palaeolithic life-ways and the movement toward new economical and social spheres, it is important to bridge the gaps in our current knowledge of the spatial and temporal trends in settlement patterns associated with it. Our aim is thus to attempt a reconstruction of the function of Bir el-Maksur and place it within the larger framework of the PPNA. In this respect, and although hindered by post depositional processes as well as by the restricted extent of the studied area, these excavations illustrate important new data concerning the occupation of the Lower Galilee during this important period.Cet article livre les rĂ©sultats de la fouille de sauvetage effectuĂ©e Ă  Bir el-Maksur, un site du NĂ©olithique prĂ©-cĂ©ramique A (PPNA) situĂ© en Basse GalilĂ©e, dans le nord d’IsraĂ«l, oĂč a Ă©tĂ© mise au jour une vaste occupation avec de riches assemblages. MalgrĂ© l’absence de structures architecturales claires, les nombreux artefacts permettent de reconstituer une variĂ©tĂ© d’activitĂ©s : le traitement de ressources vĂ©gĂ©tales et fauniques et leur consommation, une production lithique in situ et des procĂ©dĂ©s pyrotechniques Ă  grande Ă©chelle. Une sĂ©pulture secondaire complexe de deux individus, accompagnĂ©s de ce qui pourrait ĂȘtre des objets funĂ©raires (principalement outillage de mouture), indique aussi l’existence d’activitĂ©s socioculturelles plus complexes. Les fouilles et les assemblages retrouvĂ©s sont prĂ©sentĂ©s avec une analyse des activitĂ©s associĂ©es et de leur signification. Le NĂ©olithique reprĂ©sente un mouvement vers de nouvelles sphĂšres Ă©conomiques et sociales, mais il est important de combler les lacunes dans notre connaissance actuelle des modes de peuplement liĂ©s Ă  ce mouvement. Notre objectif est donc de reconstituer la fonction de Bir el-Maksur et replacer ce site dans le cadre chrono-culturel du PPNA. À cet Ă©gard et malgrĂ© les processus taphonomiques, ainsi que la superficie restreinte de la zone Ă©tudiĂ©e, ces fouilles apportent des donnĂ©es nouvelles significatives sur l’occupation de la Basse GalilĂ©e au cours de cette pĂ©riode importante.Malinsky-Buller Ariel, Aladjem Emil, Givol-Barzilai Yael, Bonnes Doron, Goren Yuval, Yeshurun Reuven, Birkenfeld Michal. Another piece in the puzzle – A new PPNA site at Bir el-Maksur (Northern Israel). In: PalĂ©orient, 2013, vol. 39, n°2. pp. 155-172

    Pediatric psychiatric emergency rooms during COVID-19: a multi-center study

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    Abstract Background The COVID-19 (SARS-CoV-2) pandemic has been a major stressor for the mental health and well-being of children and adolescents. Surveys and reports from hotlines indicate a significant rise in mental health problems. As the psychiatric emergency room (ER) is a first-line free-of-charge facility for psychiatric emergencies, we expected to see a significant increase in visits, specifically of new patients suffering from anxiety, depression, or stress-related disorders. Methods Data from two psychiatric hospital ERs and one general hospital were included. All visits of children and adolescents from the computerized files between March and December of 2019 were analyzed anonymously and compared to the same months in 2020, using multilevel linear modeling. Results There was a significant decline in the total number of visits (p = .017), specifically among those diagnosed as suffering from stress-related, anxiety, and mood disorder groups (p = .017), and an incline in the proportion of visits of severe mental disorders (p = .029). Discussion The limited use of child and adolescent psychiatric emergency facilities during the pandemic highlights the importance of tele-psychiatry as part of emergency services. It also suggests the importance of the timeline of the emergence of clinically relevant new psychiatric diagnoses related to the pandemic. Future studies are needed to establish the long-term effects of the pandemic and the expeditious use of tele-psychiatry

    MicroRNA expression detected by oligonucleotide microarrays: System establishment and expression profiling in human tissues

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    MicroRNAs (MIRs) are a novel group of conserved short ∌22 nucleotide-long RNAs with important roles in regulating gene expression. We have established a MIR-specific oligonucleotide microarray system that enables efficient analysis of the expression of the human MIRs identified so far. We show that the 60-mer oligonucleotide probes on the microarrays hybridize with labeled cRNA of MIRs, but not with their precursor hairpin RNAs, derived from amplified, size-fractionated, total RNA of human origin. Signal intensity is related to the location of the MIR sequences within the 60-mer probes, with location at the 5â€Č region giving the highest signals, and at the 3â€Č end, giving the lowest signals. Accordingly, 60-mer probes harboring one MIR copy at the 5â€Č end gave signals of similar intensity to probes containing two or three MIR copies. Mismatch analysis shows that mutations within the MIR sequence significantly reduce or eliminate the signal, suggesting that the observed signals faithfully reflect the abundance of matching MIRs in the labeled cRNA. Expression profiling of 150 MIRs in five human tissues and in HeLa cells revealed a good overall concordance with previously published results, but also with some differences. We present novel data on MIR expression in thymus, testes, and placenta, and have identified MIRs highly enriched in these tissues. Taken together, these results highlight the increased sensitivity of the DNA microarray over other methods for the detection and study of MIRs, and the immense potential in applying such microarrays for the study of MIRs in health and disease
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