This study investigates the potentially facilitative effects of internal and external attention-drawing devices-output and visual input enhancement-on the acquisition of English relativization by adult English as a second language (ESL) learners. Specifically, the study addresses: (a) whether the act of producing output promotes noticing of formal elements in the target language (TL) input and affects subsequent learning of the form; and (b) whether such outputinduced noticing and learning, if any, would be the same as that effected by visual input enhancement designed to draw learners' attention to problematic form features in the input. These questions were examined in a controlled experimental study in which the requirements of output and exposure to enhanced input were systematically varied. A computer-assisted reconstruction and reading task was used as the vehicle of presentation of the target input materials. The major findings are: (a) Those engaged in output-input activities outperformed those exposed to the same input for the sole purpose of comprehension in learning gains; (b) those who received visual An earlier version of this paper was presented at the annual meeting of the American Association for Applied Linguistics held in St. Louis, MO, in February of 2001. This paper is based on part of the author's doctoral dissertation, which was completed at Georgetown University. I am thankful to Catherine Doughty for her guidance throughout the entire process of my research project. My thanks also go to Jeff Connor-Linton and Cristina Sanz for their critical comments and encouragement. Thanks are also due to a number of people who were directly or indirectly involved in this research project, including the directors, teachers, and students of the participating ESL programs as well as people who were kindly involved in the creation, execution, and assessment of the tests and tasks used in the study. Finally, I wish to thank the anonymous SSLA reviewers for their helpful comments and insights.

Chromatin reorganization plays an important role in DNA repair, apoptosis, and cell cycle checkpoints. Among proteins involved in chromatin reorganization, TIP60 histone acetyltransferase has been shown to play a role in DNA repair and apoptosis. However, how TIP60 regulates chromatin reorganization in the response of human cells to DNA damage is largely unknown. Here, we show that ionizing irradiation induces TIP60 acetylation of histone H2AX, a variant form of H2A known to be phosphorylated following DNA damage. Furthermore, TIP60 regulates the ubiquitination of H2AX via the ubiquitin-conjugating enzyme UBC13, which is induced by DNA damage. This ubiquitination of H2AX requires its prior acetylation. We also demonstrate that acetylation-dependent ubiquitination by the TIP60-UBC13 complex leads to the release of H2AX from damaged chromatin. We conclude that the sequential acetylation and ubiquitination of H2AX by TIP60-UBC13 promote enhanced histone dynamics, which in turn stimulate a DNA damage response.Chromatin reorganization by histone modification and mobilization plays a crucial role in DNA metabolism, including replication, transcription, and repair. It appears that histone modification and mobilization can reorganize chromatin to allow DNA repair machinery to access damaged chromosomal DNA (11,29,52,56,57).H2AX is a histone variant that differs from H2A at various amino acid residues along the entire protein and in its Cterminal extensions. H2AX is phosphorylated after the induction of DNA double-strand breaks (DSBs), and the phosphorylated H2AX (␥-H2AX) participates in focus formation at sites of DNA damage. After induction of DSBs, the MRN complex (MRE11, RAD50, and NBS1) binds to broken DNA ends and recruits active ATM, ATR, and/or DNA protein kinase, resulting in the initial phosphorylation of H2AX (32,38,40). MDC1 then associates with ␥-H2AX and recruits additional activated ATM to the sites of DSBs (23,46). This positive feedback loop leads to the expansion of the ␥-H2AX region surrounding DSBs and provides docking sites for many DNA damage and repair proteins, including the MRN complex, 53BP1, and BRCA1 (5, 6, 46). ␥-H2AX plays a role in the accumulation but not in the initial recruitment of repair factors such as the MRN complex, 53BP1, and BRCA1 (10, 63). Therefore, modifications of H2AX other than phosphorylation could play a role in the initial step of the DNA damage response.Until recently, the biological significance of ubiquitination in the DNA damage response has been unclear. H2B ubiquitination regulates the damage checkpoint response (15). H2A is ubiquitinated during the response to UV-induced DNA damage (8). UV-induced DNA damage also causes the ubiquitination of histones H3 and H4, resulting in their release from chromatin (60). Interestingly, ubiquitin-conjugated proteins appear to be accumulated at sites of DSBs, forming nuclear foci like ␥-H2AX (34). These findings raise the possibility that histone ubiquitination is also involved in the reorganization of chromatin in response to D...

Following an initial investigation (Izumi, Bigelow, Fujiwara, & Fearnow, 1999), this study examines the noticing function of output (Swain, 1995(Swain, , 1998, namely, the activity of producing the target language that may prompt L2 learners to recognize their linguistic problems and bring relevant aspects of the L2 to their attention. Before completing (a) essay-writing tasks and (b) text reconstruction tasks, two groups of ESL learners received the same input containing numerous examples of the target form, the past hypothetical conditional in English. One group was given opportunities for output whereas the other group engaged in comprehension-based activities. Although the results indicate no unique effects of output, extended opportunities to produce output and receive relevant input were found to be crucial in improving learners' use of the grammatical structure. A closer examination of the data suggested, however, that output did not always succeed in drawing the learners' attention to the target form, a phenomenon that seems related to both learner and linguistic factors. The essay-writing tasks were found to be much more susceptible to such individual variation than were the text reconstruction tasks. Further research is necessary to more precisely specify the noticing function of output and derive effective uses of output in L2 teaching.

Rapid modulation of hippocampal synaptic plasticity by estrogen has long been a hot topic, but analysis of molecular mechanisms via synaptic estrogen receptors has been seriously difficult. Here, two types of independent synaptic plasticity, long-term depression (LTD) and spinogenesis, were investigated, in response to 17b-estradiol and agonists of estrogen receptors using hippocampal slices from adult male rats. Multi-electrode investigations demonstrated that estradiol rapidly enhanced LTD not only in CA1 but also in CA3 and dentate gyrus. Dendritic spine morphology analysis demonstrated that the density of thin type spines was selectively increased in CA1 pyramidal neurons within 2 h after application of 1 nM estradiol. This enhancement of spinogenesis was completely suppressed by mitogen-activated protein (MAP) kinase inhibitor. Only the estrogen receptor (ER) alpha agonist, (propyl-pyrazole-trinyl)tris-phenol (PPT), induced the same enhancing effect as estradiol on both LTD and spinogenesis in the CA1. The ERbeta agonist, (4-hydroxyphenyl)-propionitrile (DPN), suppressed LTD and did not affect spinogenesis. Because the mode of synaptic modulations by estradiol was mostly the same as that by the

Wnt-5a is a representative ligand that activates a β-catenin-independent pathway in Wnt signalling. In the present paper, the roles of the post-translational modifications in the actions of Wnt-5a were investigated. We found that Wnt-5a is modified with palmitate at Cys 104 and glycans at Asn 114 , Asn 120 , Asn 311 and Asn 325 . The palmitoylation was not essential for the secretion of Wnt-5a, but was necessary for its ability to suppress Wnt-3a-dependent Tcell factor transcriptional activity and to stimulate cell migration. Wnt-5a activated focal adhesion kinase and this activation also required palmitoylation. Wild-type Wnt-5a induced the internalization of Fz (Frizzled) 5, but a Wnt-5a mutant that lacks the palmitoylation site did not. Furthermore, the binding of Wnt5a to the extracellular domain of Fz5 required palmitoylation of Wnt-5a. These results indicate that palmitoylation of Wnt-5a is important for the triggering of signalling at the cell surface level and, therefore, that the lipid-unmodified form of Wnt-5a cannot activate intracellular signal cascades. In contrast, glycosylation was necessary for the secretion of Wnt-5a, but not essential for the actions of Wnt-5a. Thus the post-translational palmitoylation and glycosylation of Wnt-5a are important for the actions and secretion of Wnt-5a.