Orthographic effects on L2 production and L2 proficiency in ESL learners with non-alphabetic and orthographically opaque L1

This study examined the role of first language (L1) transparency in intra-orthographic effects on second language (L2) pronunciation by studying L2 learners with a non-alphabetic and orthographically opaque L1 and an alphabetic L2. Relations between orthographic effects, phonological awareness, and L2 proficiency were examined. Fifty-four Cantonese-speaking English as a second language (ESL) learners participated in Experiment 1 with orthographic effect tasks (homophone and silent-letter read-aloud) and phonological awareness tasks. Thirty Cantonese-speaking and 30 Mandarin-speaking ESL learners participated in Experiment 2 with orthographic effect tasks and an L2 proficiency task. The L2 pronunciation of Cantonese and Mandarin participants was subjected to intra-orthographic effects. Phonological awareness and L2 proficiency were associated with less orthographic effects on L2 pronunciation in Cantonese participants. Mandarin participants did not subject to more orthographic effects than Cantonese participants when controlling L2 proficiency, implying that shared alphabetic scripts between Pinyin and English did not interfere with L2 production. Overall, transferring the L1 reading strategy that relies on orthography to decode phonology to L2 reading seemed not to be the key mechanism behind intra-orthographic effects. L2 graphemes were likely to be decoded with incorrect L2 grapheme-to-phoneme correspondences, resulting in intra-orthographic effects

SCRIBBLE is required for pregnancy-induced alveologenesis in the adult mammary gland

The cell polarity protein SCRIB is a critical regulator of polarization, cell migration and tumourigenesis. Whereas SCRIB is known to regulate early stages of mouse mammary gland development, its function in the adult gland is not known. Using an inducible RNAi mouse model for downregulating SCRIB expression, we report an unexpected role for SCRIB as a positive regulator of cell proliferation during pregnancy associated mammary alveologenesis. SCRIB was required in the epithelial cell compartment of the mammary gland. Lack of SCRIB attenuated prolactin-induced activation of the JAK2/STAT5 signaling pathway. In addition, loss of SCRIB resulted in the downregulation of PRLR at cell surface and accumulation in intracellular structures that express markers of the Golgi apparatus and the recycling endosome. Unlike its role in virgin gland as a negative regulator cell proliferation, SCRIB is a positive regulator of mammary epithelial cell proliferation during pregnancy

Enzymatic Ligation Creates Discrete Multi-Nanoparticle Building Blocks for Self-Assembly

Enzymatic ligation of discrete nanoparticle?DNA conjugates creates nanoparticle dimer and trimer structures in which the nanoparticles are linked by single-stranded DNA, rather than double-stranded DNA as in previous experiments. Ligation is verified by agarose gel and small-angle X-ray scattering. This capability is utilized in two ways: first to create a new class of multiparticle building blocks for nanoscale self-assembly; second to develop a system which can amplify a population of discrete nanoparticle assemblies

Tai-Chi for Residential Patients with Schizophrenia on Movement Coordination, Negative Symptoms, and Functioning: A Pilot Randomized Controlled Trial

Objective. Patients with schizophrenia residing at institutions often suffer from negative symptoms, motor, and functional impairments more severe than their noninstitutionalized counterparts. Tai-chi emphasizes body relaxation, alertness, and movement coordination with benefits to balance, focus, and stress relief. This pilot study explored the efficacy of Tai-chi on movement coordination, negative symptoms, and functioning disabilities towards schizophrenia. Methods. A randomized waitlist control design was adopted, where participants were randomized to receive either the 6-week Tai-chi program and standard residential care or only the latter. 30 Chinese patients with schizophrenia were recruited from a rehabilitation residency. All were assessed on movement coordination, negative symptoms, and functional disabilities at baseline, following intervention and 6 weeks after intervention. Results. Tai-chi buffered from deteriorations in movement coordination and interpersonal functioning, the latter with sustained effectiveness 6 weeks after the class was ended. Controls showed marked deteriorations in those areas. The Tai-chi group also experienced fewer disruptions to life activities at the 6-week maintenance. There was no significant improvement in negative symptoms after Tai-chi. Conclusions. This study demonstrated encouraging benefits of Tai-chi in preventing deteriorations in movement coordination and interpersonal functioning for residential patients with schizophrenia. The ease of implementation facilitates promotion at institutional psychiatric services

Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study

Objectives To validate the clinical efficacy and practical feasibility of massively parallel maternal plasma DNA sequencing to screen for fetal trisomy 21 among high risk pregnancies clinically indicated for amniocentesis or chorionic villus sampling

Cag rnas induce dna damage and apoptosis by silencing nudt16 expression in polyglutamine degeneration

DNA damage plays a central role in the cellular pathogenesis of polyglutamine (polyQ) diseases, including Huntington's disease (HD). In this study, we showed that the expression of untranslatable expanded CAG RNA per se induced the cellular DNA damage response pathway. By means of RNA sequencing (RNA-seq), we found that expression of the Nudix hydrolase 16 (NUDT16) gene was down-regulated in mutant CAG RNA-expressing cells. The loss of NUDT16 function results in a misincorporation of damaging nucleotides into DNAs and leads to DNA damage. We showed that small CAG (sCAG) RNAs, species generated from expanded CAG transcripts, hybridize with CUG-containing NUDT16 mRNA and form a CAG-CUG RNA heteroduplex, resulting in gene silencing of NUDT16 and leading to the DNA damage and cellular apoptosis. These results were further validated using expanded CAG RNAexpressing mouse primary neurons and in vivo R6/2 HD transgenic mice. Moreover, we identified a bisamidinium compound, DB213, that interacts specifically with the major groove of the CAG RNA homoduplex and disfavors the CAG-CUG heteroduplex formation. This action subsequently mitigated RNA-induced silencing complex (RISC)-dependent NUDT16 silencing in both in vitro cell and in vivo mouse disease models. After DB213 treatment, DNA damage, apoptosis, and locomotor defects were rescued in HD mice. This work establishes NUDT16 deficiency by CAG repeat RNAs as a pathogenic mechanism of polyQ diseases and as a potential therapeutic direction for HD and other polyQ diseases

Cbl Enforces Vav1 Dependence and a Restricted Pathway of T Cell Development

Extensive studies of pre-TCR- and TCR-dependent signaling have led to characterization of a pathway deemed essential for efficient T cell development, and comprised of a cascade of sequential events involving phosphorylation of Lck and ZAP-70, followed by phosphorylation of LAT and SLP-76, and subsequent additional downstream events. Of interest, however, reports from our lab as well as others have indicated that the requirements for ZAP-70, LAT, and SLP-76 are partially reversed by inactivation of c-Cbl (Cbl), an E3 ubiquitin ligase that targets multiple molecules for ubiquitination and degradation. Analysis of signaling events in these Cbl knockout models, including the recently reported analysis of SLP-76 transgenes defective in interaction with Vav1, suggested that activation of Vav1 might be a critical event in alternative pathways of T cell development. To extend the analysis of signaling requirements for thymic development, we have therefore assessed the effect of Cbl inactivation on the T cell developmental defects that occur in Vav1-deficient mice. The defects in Vav1-deficient thymic development, including a marked defect in DN3-DN4 transition, were completely reversed by Cbl inactivation, accompanied by enhanced phosphorylation of PLC-γ1 and ERKs in response to pre-TCR/TCR cross-linking of Vav1-/-Cbl-/- DP thymocytes. Taken together, these results suggest a substantially modified paradigm for pre-TCR/TCR signaling and T cell development. The observed consensus pathways of T cell development, including requirements for ZAP-70, LAT, SLP-76, and Vav1, appear to reflect the restriction by Cbl of an otherwise much broader set of molecular pathways capable of mediating T cell development