Hyperreactivity to weak acoustic stimuli and prolonged acoustic startle latency in children with autism spectrum disorders

BACKGROUND: People with autism spectrum disorders (ASD) are known to have enhanced auditory perception, however, acoustic startle response to weak stimuli has not been well documented in this population. The objectives of this study are to evaluate the basic profile of acoustic startle response, including peak startle latency and startle magnitude to weaker stimuli, in children with ASD and typical development (TD), and to evaluate their relationship to ASD characteristics. METHODS: We investigated acoustic startle response with weak and strong acoustic stimuli in 12 children with ASD and 28 children with TD, analyzing the relationship between startle measures and quantitative autistic traits assessed with the Social Responsiveness Scale (SRS). The electromyographic activity of the left orbicularis oculi muscle to acoustic stimuli of 65 to 115 dB sound pressure level (SPL), in increments of 5 dB, was measured to evaluate acoustic startle response. The average eyeblink magnitude for each acoustic stimuli intensity and the average peak startle latency of acoustic startle response were evaluated. RESULTS: The magnitude of the acoustic startle response to weak stimuli (85 dB or smaller) was greater in children with ASD. The peak startle latency was also prolonged in individuals with ASD. The average magnitude of the acoustic startle response for stimulus intensities greater than 85 dB was not significantly larger in the ASD group compared with the controls. Both greater startle magnitude in response to weak stimuli (particularly at 85 dB) and prolonged peak startle latency were significantly associated with total scores, as well as several subscales of the SRS in the whole sample. We also found a significant relationship between scores on the social cognition subscale of the SRS and the average magnitude of the acoustic startle response for stimulus intensities of 80 and 85 dB in the TD group. CONCLUSIONS: Children with ASD exhibited larger startle magnitude to weak stimuli and prolonged peak startle latency. These startle indices were related to several characteristics of ASD. A comprehensive investigation of acoustic startle response, including the magnitude of startle responses to weak stimuli and peak startle latency, might further our understanding of the neurophysiological impairments underlying ASD

コミュニケーション ゲンゴ カツドウ ノ ジュクタツド オ アラワス JF Can-do ノ サクセイ ト ヒョウカ CEFR ノ A2 B1 レベル ニ モトヅイテ

日本語教育において言語熟達度を表す共通の枠組みがないという状況をふまえ、国際交流基金は、 CEFR に基づいた日本語の熟達度を表す能力記述文としてJF Can-do を開発中である。本稿では、JF Cando 開発の第1段階であるA2およびB1レベルのCan-do 作成と、その記述に対する現場教師の評価に ついて述べる。評価の観点は、(1)レベルが妥当か、(2)言語活動のカテゴリーが妥当か、(3)記述はわかり やすいか、(4)教室活動等がイメージしやすいか、の4点である。作成過程において現場教師による評価 を取り入れたことにより、教育現場で使いやすいCan-do を記述する際に考慮すべき点について有益な フィードバックを得た。その一方で、Can-do を十分に理解し、枠組みを共有していくためには、継続 したワークショップ等の実施が重要であることもわかった。Given that there is no common framework for Japanese language proficiency, The Japan Foundation is developing Japanese language proficiency descriptors (“JF Can-do”) based on the CEFR illustrative descriptors. This paper reports on the first stage of the development of JF Can-do (for levels A 2 and B 1) and the evaluation of the descriptions by teachers. The points of the evaluation are as follows : 1) validity of the proficiency level, 2) appropriateness of the language activity category, 3) clarity of descriptions, and 4) ease in visualizing classroom activities. Useful feedback was gained by carrying out the teachers\u27 evaluation in the process of developing JF Can-do that are easy to use in classroom situations. Meanwhile, the results also showed that continued workshops were needed in order for the teachers to fully understand and share the framework

Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11

PICT1 (also known as GLTSCR2) is considered a tumor suppressor because it stabilizes phosphatase and tensin homolog (PTEN), but individuals with oligodendrogliomas lacking chromosome 19q13, where PICT1 is located, have better prognoses than other oligodendroglioma patients. To clarify the function of PICT1, we generated Pict1-deficient mice and embryonic stem (ES) cells. Pict1 is a nucleolar protein essential for embryogenesis and ES cell survival. Even without DNA damage, Pict1 loss led to p53-dependent arrest of cell cycle phase G1 and apoptosis. Pict1-deficient cells accumulated p53, owing to impaired Mdm2 function. Pict1 binds Rpl11, and Rpl11 is released from nucleoli in the absence of Pict1. In Pict1-deficient cells, increased binding of Rpl11 to Mdm2 blocks Mdm2-mediated ubiquitination of p53. In human cancer, individuals whose tumors express less PICT1 have better prognoses. When PICT1 is depleted in tumor cells with intact P53 signaling, the cells grow more slowly and accumulate P53. Thus, PICT1 is a potent regulator of the MDM2-P53 pathway and promotes tumor progression by retaining RPL11 in the nucleolu

ATM Modulates the Loading of Recombination Proteins onto a Chromosomal Translocation Breakpoint Hotspot

Chromosome translocations induced by DNA damaging agents, such as ionizing radiation and certain chemotherapies, alter genetic information resulting in malignant transformation. Abrogation or loss of the ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, increases the incidence of chromosome translocations. However, how ATM protects cells from chromosome translocations is still unclear. Chromosome translocations involving the MLL gene on 11q23 are the most frequent chromosome abnormalities in secondary leukemias associated with chemotherapy employing etoposide, a topoisomerase II poison. Here we show that ATM deficiency results in the excessive binding of the DNA recombination protein RAD51 at the translocation breakpoint hotspot of 11q23 chromosome translocation after etoposide exposure. Binding of Replication protein A (RPA) and the chromatin remodeler INO80, which facilitate RAD51 loading on damaged DNA, to the hotspot were also increased by ATM deficiency. Thus, in addition to activating DNA damage signaling, ATM may avert chromosome translocations by preventing excessive loading of recombinational repair proteins onto translocation breakpoint hotspots