437 research outputs found

    The Varieties of Pathways to Dysfluent Reading Comparing Subtypes of Children With Dyslexia at Letter, Word, and Connected Text Levels of Reading

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    The majority of work on the double-deficit hypothesis (DDH) of dyslexia has been done at the letter and word levels of reading. Key research questions addressed in this study are (a) do readers with different subtypes of dyslexia display differences in fluency at particular reading levels (e.g., letter, word, and connected text)? and (b) do children with dyslexia identified by either low-achievement or ability–achievement discrepancy criteria show similar differences when classified by the DDH? To address these questions, the authors assessed a sample of 158 children with severe reading impairments in second and third grades on an extensive battery and classified them into three reader subtypes using the DDH. The results demonstrated that the three DDH subtypes exhibited differences in fluency at different levels of reading (letter, word, and connected text), underscoring the separate reading profiles of these subtypes and the different possible routes to dysfluency in reading disabilities. Furthermore, the results suggest that the different patterns among DDH subtypes are primarily driven by the ability–achievement discrepancy group. The implications of these findings are discussed for intervention, reading theory, and a more refined understanding of heterogeneity

    The CIL-1 PI 5-Phosphatase Localizes TRP Polycystins to Cilia and Activates Sperm in C. elegans

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    SummaryBackgroundC. elegans male sexual behaviors include chemotaxis and response to hermaphrodites, backing, turning, vulva location, spicule insertion, and sperm transfer, culminating in cross-fertilization of hermaphrodite oocytes with male sperm. The LOV-1 and PKD-2 transient receptor potential polycystin (TRPP) complex localizes to ciliated endings of C. elegans male-specific sensory neurons and mediates several aspects of male mating behavior. TRPP complex ciliary localization and sensory function are evolutionarily conserved. A genetic screen for C. elegans mutants with PKD-2 ciliary localization (Cil) defects led to the isolation of a mutation in the cil-1 gene.ResultsHere, we report that a phosphoinositide (PI) 5-phosphatase, CIL-1, regulates TRPP complex ciliary receptor localization and sperm activation. cil-1 does not regulate the localization of other ciliary proteins, including intraflagellar transport (IFT) components, sensory receptors, or other TRP channels in different cell types. Rather, cil-1 specifically controls TRPP complex trafficking in male-specific sensory neurons and does so in a cell-autonomous fashion. In these cells, cil-1 is required for normal PI(3)P distribution, indicating that a balance between PI(3,5)P2 and PI(3)P is important for TRPP localization. cil-1 mutants are infertile because of sperm activation and motility defects. In sperm, the CIL-1 5-phosphatase and a wortmannin-sensitive PI 3-kinase act antagonistically to regulate the conversion of sessile spermatids into motile spermatozoa, implicating PI(3,4,5)P3 signaling in nematode sperm activation.ConclusionOur studies identify the CIL-1 5-phosphatase as a key regulator of PI metabolism in cell types that are important in several aspects of male reproductive biology

    Tire Art: Environmental Education through Science, Visual and Language Arts

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    This international project examined the use of an arts-integrated approach to teaching and learning 8th grade science and language art. It involved two arts faculty collaborating with classroom teachers in the US and South Korea. In the context of the "Tire Art project”, students and teachers were guided through several 2D and 3D creative interactions emphasizing innovative uses for recycled car tires and bicycle wheels. In this paper, authors discuss the learning that happened through the arts, and the learning that happened (by teachers) of arts integration methods. It is to be noted that integration is not only about the arts. In fact, if teachers take advantage of this approach, they will discover more connections and bridges between various non-art subjects. When teachers are as affected by innovative approaches as the students, they often feel more confident and empowered in their professional competencies

    Post-Transcriptional Dysregulation by miRNAs Is Implicated in the Pathogenesis of Gastrointestinal Stromal Tumor [GIST]

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    peer-reviewedIn contrast to adult mutant gastrointestinal stromal tumors [GISTs], pediatric/wild-type GISTs remain poorly understood overall, given their lack of oncogenic activating tyrosine kinase mutations. These GISTs, with a predilection for gastric origin in female patients, show limited response to therapy with tyrosine kinase inhibitors and generally pursue a more indolent course, but still may prove fatal. Defective cellular respiration appears to underpin tumor development in these wild-type cases, which as a group lack expression of succinate dehydrogenase [SDH] B, a surrogate marker for respiratory chain metabolism. Yet, only a small subset of the wild-type tumors show mutations in the genes coding for the SDH subunits [SDHx]. To explore additional pathogenetic mechanisms in these wild-type GISTs, we elected to investigate posttranscriptional regulation of these tumors by conducting microRNA (miRNA) profiling of a mixed cohort of 73 cases including 18 gastric pediatric wild-type, 25 (20 gastric, 4 small bowel and 1 retroperitoneal) adult wild-type GISTs and 30 gastric adult mutant GISTs. By this approach we have identified distinct signatures for GIST subtypes which correlate tightly with clinico-pathological parameters. A cluster of miRNAs on 14q32 show strikingly different expression patterns amongst GISTs, a finding which appears to be explained at least in part by differential allelic methylation of this imprinted region. Small bowel and retroperitoneal wild-type GISTs segregate with adult mutant GISTs and express SDHB, while adult wildtype gastric GISTs are dispersed amongst adult mutant and pediatric wild-type cases, clustering in this situation on the basis of SDHB expression. Interestingly, global methylation analysis has recently similarly demonstrated that these wild-type, SDHB-immunonegative tumors show a distinct pattern compared with KIT and PDGFRA mutant tumors, which as a rule do express SDHB. All cases with Carney triad within our cohort cluster together tightly.Funding was obtained from the Medical Research Charities Group (http://www.mrcg.ie/) and Health Research Board of Ireland (http://www.hrb.ie) (MO’S), The Children’s Medical and Research Foundation (http://www.cmrf.org) (MO’S), the GIST Cancer Awareness Foundation [GCAF] (http://www. gistawareness.org/)(MO’S), and research grants from the Life Raft Group (http://www.liferaftgroup.org/)(MD-R) and from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (http://www.fwo.be/)(grant # G.0286.05 MD-R)

    Gemstone: Quality in Learning for a Collaborative Academic/Library Instruction Program

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    Poster presented on June 4, 2009 at the 2009 International Association of Technological University Libraries (IATUL) conference, Leuven, Belgium (June 1-4, 2009)This poster focuses on University of Maryland librarians’ participation in an innovative, collaborative program where instruction extends beyond a typical library session, providing students with a quality learning experience over the course of four years. The program, called Gemstone, is an interdisciplinary honors research program and involves collaboration between librarians, faculty, program staff, and undergraduate students. During the first year of the program, the students attend classes that help them prepare for their research. After forming research teams, they spend the next three years designing and conducting a research project that focuses on the intersection of science and technology with society. This experience facilitates the development of research, teamwork, communication, and leadership skills, and culminates in the students’ defense of their thesis, orally and in writing, to a panel of experts. Librarians are involved in the first year of the program through a class called GEMS 100. The librarians teach a session of the class where they introduce research tools and lead the students in critical thinking exercises to turn their potential topic ideas into research questions. During the remainder of the program, the librarians partner with a particular team. That partnership includes helping the students with research strategies on an informal basis, reviewing and critiquing proposals and presentations, and attending the Junior Colloquia and final Team Thesis Conference. The librarians and faculty mentors assigned to each group also meet several times a year to compare notes about improving the quality of assistance for the students' research efforts. By having librarians work closely with them throughout the research process, students further benefit from the advice, feedback, and expertise in research skills that the librarians provide. Thus, the librarians have the opportunity to provide quality, hands-on service over an extended period of time leading to an enriched learning experience

    A variable near-infrared counterpart to the neutron-star low-mass X-ray binary 4U 1705-440

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    We report the discovery of a near-infrared (nIR) counterpart to the persistent neutron-star low-mass X-ray binary 4U 1705-440, at a location consistent with its recently determined Chandra X-ray position. The nIR source is highly variable, with K_s-band magnitudes varying between 15.2 and 17.3 and additional J- and H-band observations revealing color variations. A comparison with contemporaneous X-ray monitoring observations shows that the nIR brightness correlates well with X-ray flux and X-ray spectral state. We also find possible indications for a change in the slope of the nIR/X-ray flux relation between different X-ray states. We discuss and test various proposed mechanisms for the nIR emission from neutron-star low-mass X-ray binaries and conclude that the nIR emission in 4U 1705-440 is most likely dominated by X-ray heating of the outer accretion disk and the secondary star.Comment: Accepted for publication in Ap

    SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion.

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    The secretory pathway of eukaryotic cells packages cargo proteins into COPII-coated vesicles for transport from the endoplasmic reticulum (ER) to the Golgi. We now report that complete genetic deficiency for the COPII component SEC24A is compatible with normal survival and development in the mouse, despite the fundamental role of SEC24 in COPII vesicle formation and cargo recruitment. However, these animals exhibit markedly reduced plasma cholesterol, with mutations in Apoe and Ldlr epistatic to Sec24a, suggesting a receptor-mediated lipoprotein clearance mechanism. Consistent with these data, hepatic LDLR levels are up-regulated in SEC24A-deficient cells as a consequence of specific dependence of PCSK9, a negative regulator of LDLR, on SEC24A for efficient exit from the ER. Our findings also identify partial overlap in cargo selectivity between SEC24A and SEC24B, suggesting a previously unappreciated heterogeneity in the recruitment of secretory proteins to the COPII vesicles that extends to soluble as well as trans-membrane cargoes. DOI:http://dx.doi.org/10.7554/eLife.00444.001
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