67 research outputs found

    Loss of ATM kinase activity leads to embryonic lethality in mice

    Get PDF
    Ataxia telangiectasia (A-T) mutated (ATM) is a key deoxyribonucleic acid (DNA) damage signaling kinase that regulates DNA repair, cell cycle checkpoints, and apoptosis. The majority of patients with A-T, a cancer-prone neurodegenerative disease, present with null mutations in Atm. To determine whether the functions of ATM are mediated solely by its kinase activity, we generated two mouse models containing single, catalytically inactivating point mutations in Atm. In this paper, we show that, in contrast to Atm-null mice, both D2899A and Q2740P mutations cause early embryonic lethality in mice, without displaying dominant-negative interfering activity. Using conditional deletion, we find that the D2899A mutation in adult mice behaves largely similar to Atm-null cells but shows greater deficiency in homologous recombination (HR) as measured by hypersensitivity to poly (adenosine diphosphate-ribose) polymerase inhibition and increased genomic instability. These results may explain why missense mutations with no detectable kinase activity are rarely found in patients with classical A-T. We propose that ATM kinase-inactive missense mutations, unless otherwise compensated for, interfere with HR during embryogenesis

    Empathy predicts false belief reasoning ability: evidence from the N400

    Get PDF
    Interpreting others’ actions relies on an understanding of their current mental state. Emerging research has begun to identify a number of factors that give rise to individual differences in this ability. We report an event-related brain potential study where participants ( N = 28) read contexts that described a character having a true belief (TB) or false belief (FB) about an object’s location. A second sentence described where that character would look for the object. Critically, this sentence included a sentence-final noun that was either consistent or inconsistent with the character’s belief. Participants also completed the Empathy Quotient questionnaire. Analysis of the N400 revealed that when the character held a TB about the object’s location, the N400 waveform was more negative-going for belief inconsistent vs belief consistent critical words. However, when the character held an FB about the object’s location the opposite pattern was found. Intriguingly, correlations between the N400 inconsistency effect and individuals’ empathy scores showed a significant correlation for FB but not TB. This suggests that people who are high in empathy can successfully interpret events according to the character’s FB, while low empathizers bias their interpretation of events to their own egocentric view

    Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

    Get PDF
    [This corrects the article DOI: 10.1186/s13054-016-1208-6.]
    corecore