Developmental changes in the role of different metalinguistic awareness skills in Chinese reading acquisition from preschool to third grade

Copyright @ 2014 Wei et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The present study investigated the relationship between Chinese reading skills and metalinguistic awareness skills such as phonological, morphological, and orthographic awareness for 101 Preschool, 94 Grade-1, 98 Grade-2, and 98 Grade-3 children from two primary schools in Mainland China. The aim of the study was to examine how each of these metalinguistic awareness skills would exert their influence on the success of reading in Chinese with age. The results showed that all three metalinguistic awareness skills significantly predicted reading success. It further revealed that orthographic awareness played a dominant role in the early stages of reading acquisition, and its influence decreased with age, while the opposite was true for the contribution of morphological awareness. The results were in stark contrast with studies in English, where phonological awareness is typically shown as the single most potent metalinguistic awareness factor in literacy acquisition. In order to account for the current data, a three-stage model of reading acquisition in Chinese is discussed.National Natural Science Foundation of China and Knowledge Innovation Program of the Chinese Academy of Sciences

DNA end resection by Dna2–Sgs1–RPA and its stimulation by Top3–Rmi1 and Mre11–Rad50–Xrs2

The repair of DNA double-strand breaks (DSBs) by homologous recombination requires processing of broken ends. For repair to start, the DSB must first be resected to generate a 3′-single-stranded DNA (ssDNA) overhang, which becomes a substrate for the DNA strand exchange protein, Rad51 (ref. 1). Genetic studies have implicated a multitude of proteins in the process, including helicases, nucleases and topoisomerases. Here we biochemically reconstitute elements of the resection process and reveal that it requires the nuclease Dna2, the RecQ-family helicase Sgs1 and the ssDNA-binding protein replication protein-A (RPA). We establish that Dna2, Sgs1 and RPA constitute a minimal protein complex capable of DNA resection in vitro. Sgs1 helicase unwinds the DNA to produce an intermediate that is digested by Dna2, and RPA stimulates DNA unwinding by Sgs1 in a species-specific manner. Interestingly, RPA is also required both to direct Dna2 nucleolytic activity to the 5′-terminated strand of the DNA break and to inhibit 3′ to 5′ degradation by Dna2, actions that generate and protect the 3′-ssDNA overhang, respectively. In addition to this core machinery, we establish that both the topoisomerase 3 (Top3) and Rmi1 complex and the Mre11–Rad50–Xrs2 complex (MRX) have important roles as stimulatory components. Stimulation of end resection by the Top3–Rmi1 heterodimer and the MRX proteins is by complex formation with Sgs1 (refs 5, 6), which unexpectedly stimulates DNA unwinding. We suggest that Top3–Rmi1 and MRX are important for recruitment of the Sgs1–Dna2 complex to DSBs. Our experiments provide a mechanistic framework for understanding the initial steps of recombinational DNA repair in eukaryotes

Efficient unidirectional nanoslit couplers for surface plasmons

Plasmonics is based on surface plasmon polariton (SPP) modes which can be laterally confined below the diffraction limit, thereby enabling ultracompact optical components. In order to exploit this potential, the fundamental bottleneck of poor light-SPP coupling must be overcome. In established SPP sources (using prism, grating} or nanodefect coupling) incident light is a source of noise for the SPP, unless the illumination occurs away from the region of interest, increasing the system size and weakening the SPP intensity. Back-side illumination of subwavelength apertures in optically thick metal films eliminates this problem but does not ensure a unique propagation direction for the SPP. We propose a novel back-side slit-illumination method based on drilling a periodic array of indentations at one side of the slit. We demonstrate that the SPP running in the array direction can be suppressed, and the one propagating in the opposite direction enhanced, providing localized unidirectional SPP launching.Comment: 13 pages, 4 figure

3D human skin bioprinting: a view from the bio side

Based on the 3D printing technologies and the concepts developed in tissue engineering during the last decades, 3D bioprinting is emerging as the most innovative and promising technology for the generation of human tissues and organs. In the case of skin bioprinting, thanks to the research process carried out during the last years, interfollicular skin has been printed with a structural and functional quality that paves the way for clinical and industrial applications. This review analyzes the present achievements and the future improvements that this area must bring about if bioprinted skin is to become widely used. We have made an effort to integrate the technological and the biological/biomedical sides of the subject.We thank the Spanish Fundación Ramón Areces for its continuous support. This work was partially supported by grant DPI2014-61887-EXP from the Spanish Ministerio de Economía y Competitividad

Time delay between images of the lensed quasar UM673

We study brightness variations in the double lensed quasar UM673 (Q0142-100) with the aim of measuring the time delay between its two images. In the paper we combine our previously published observational data of UM673 obtained during the 2003 - 2005 seasons at the Maidanak Observatory with archival and recently observed Maidanak and CTIO UM673 data. We analyze the V, R and I-band light curves of the A and B images of UM673, which cover ten observational seasons from August 2001 to November 2010. We also analyze the time evolution of the difference in magnitudes between images A and B of UM673 over more than ten years. We find that the quasar exhibits both short-term (with amplitude of \sim 0.1 mag in the R band) and high-amplitude (\sim 0.3 mag) long-term variability on timescales of about several months and several years, respectively. These brightness variations are used to constrain the time delay between the images of UM673. From cross-correlation analysis of the A and B quasar light curves and error analysis we measure the mean time delay and its error of 89 \pm11 days. Given the input time delay of 88 days, the most probable value of the delay that can be recovered from light curves with the same statistical properties as the observed R-band light curves of UM673 is 95{+5/-16}{+14/-29} days (68 and 95 % confidence intervals). Analysis of the V - I color variations and V, R and I-band magnitude differences of the quasar images does not show clear evidence of the microlensing variations between 1998 and 2010.Comment: Submitted to A&A, 11 pages, 9 figure

Epigenetics as a mechanism driving polygenic clinical drug resistance

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

Superconducting Sr2RuO4 Thin Films without Out-of-Phase Boundaries by Higher-Order Ruddlesden-Popper Intergrowth

Ruddlesden-Popper (RP) phases (An+1B n O3n+1, n = 1, 2,···) have attracted intensive research with diverse functionalities for device applications. However, the realization of a high-quality RP-phase film is hindered by the formation of out-of-phase boundaries (OPBs) that occur at terrace edges, originating from lattice mismatch in the c-axis direction with the A'B'O3 (n = ∞) substrate. Here, using strontium ruthenate RP-phase Sr2RuO4 (n = 1) as a model system, an experimental approach for suppressing OPBs was developed. By tuning the growth parameters, the Sr3Ru2O7 (n = 2) phase was formed in a controlled manner near the film-substrate interface. This higher-order RP-phase then blocked the subsequent formation of OPBs, resulting in nearly defect-free Sr2RuO4 layer at the upper region of the film. Consequently, the Sr2RuO4 thin films exhibited superconductivity up to 1.15 K, which is the highest among Sr2RuO4 films grown by pulsed laser deposition. This work paves the way for synthesizing pristine RP-phase heterostructures and exploring their unique physical properties

MutLα heterodimers modify the molecular phenotype of Friedreich ataxia

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA), the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR) MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions. Methodology/Principal Findings: To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription. Conclusions/Significance: Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription. © 2014 Ezzatizadeh et al.This article has been made available through the Brunel Open Access Publishing Fund

Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system

Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Garavaglia, Matías Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goya, María Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin