Analysis Of Textbooks For Beginning English Learners In Middle School

Research shows that it takes an average of 5-7 years for English learners to achieve academic English proficiency (Demie, 2013). Students who begin learning English in middle school have exactly 5-7 years remaining in school to achieve proficiency. This project analyzes three textbooks intended for beginning English learners in middle school in order to answer the question: Which textbook or textbooks can be recommended as a solid textbook for grammar instruction for beginning English learners in a middle school? The three textbooks were systematically analyzed for explicit instruction, samples of language, and activity types included, as well as the adherence to the scope of developmental stages of English acquisition (Fernandez, 2001; Dutro et al, 2005). Through the findings, one textbook is recommended above the others for grammar instruction

Biology of human hair: Know your hair to control it

Hair can be engineered at different levels—its structure and surface—through modification of its constituent molecules, in particular proteins, but also the hair follicle (HF) can be genetically altered, in particular with the advent of siRNA-based applications. General aspects of hair biology are reviewed, as well as the most recent contributions to understanding hair pigmentation and the regulation of hair development. Focus will also be placed on the techniques developed specifically for delivering compounds of varying chemical nature to the HF, indicating methods for genetic/biochemical modulation of HF components for the treatment of hair diseases. Finally, hair fiber structure and chemical characteristics will be discussed as targets for keratin surface functionalization

DSL ligand endocytosis physically dissociates Notch1 heterodimers before activating proteolysis can occur

Cleavage of Notch by furin is required to generate a mature, cell surface heterodimeric receptor that can be proteolytically activated to release its intracellular domain, which functions in signal transduction. Current models propose that ligand binding to heterodimeric Notch (hNotch) induces a disintegrin and metalloprotease (ADAM) proteolytic release of the Notch extracellular domain (NECD), which is subsequently shed and/or endocytosed by DSL ligand cells. We provide evidence for NECD release and internalization by DSL ligand cells, which, surprisingly, did not require ADAM activity. However, losses in either hNotch formation or ligand endocytosis significantly decreased NECD transfer to DSL ligand cells, as well as signaling in Notch cells. Because endocytosis-defective ligands bind hNotch, but do not dissociate it, additional forces beyond those produced through ligand binding must function to disrupt the intramolecular interactions that keep hNotch intact and inactive. Based on our findings, we propose that mechanical forces generated during DSL ligand endocytosis function to physically dissociate hNotch, and that dissociation is a necessary step in Notch activation

Classification and function of small open reading frames

Small open reading frames (smORFs) of 100 codons or fewer are usually - if arbitrarily - excluded from proteome annotations. Despite this, the genomes of many metazoans, including humans, contain millions of smORFs, some of which fulfil key physiological functions. Recently, the transcriptome of Drosophila melanogaster was shown to contain thousands of smORFs of different classes that actively undergo translation, which produces peptides of mostly unknown function. Here, we present a comprehensive analysis of smORFs in flies, mice and humans. We propose the existence of several functional classes of smORFs, ranging from inert DNA sequences to transcribed and translated cis-regulators of translation and peptides with a propensity to function as regulators of membrane-associated proteins, or as components of ancient protein complexes in the cytoplasm. We suggest that the different smORF classes could represent steps in gene, peptide and protein evolution. Our analysis introduces a distinction between different peptide-coding classes of smORFs in animal genomes, and highlights the role of model organisms for the study of small peptide biology in the context of development, physiology and human disease

Notch1 Deficiency Dissociates the Intrathymic Development of Dendritic Cells and T Cells

Thymic dendritic cells (DCs) form a discrete subset of bone marrow (BM)-derived cells, the function of which is to mediate negative selection of autoreactive thymocytes. The developmental origin of thymic DCs remains controversial. Although cell transfer studies support a model in which T cells and thymic DCs develop from the same intrathymic pluripotential precursor, it remains possible that these two types of cells develop from independent intrathymic precursors. Notch proteins are cell surface receptors involved in the regulation of cell fate specification. We have recently reported that T cell development in inducible Notch1-deficient mice is severely impaired at an early stage, before the expression of T cell lineage markers. To investigate whether development of thymic DCs also depends on Notch1, we have constructed mixed BM chimeric mice. We report here that thymic DC development from Notch1−/− BM precursors is absolutely normal (in terms of absolute number and phenotype) in this competitive situation, despite the absence of Notch1−/− T cells. Furthermore, we find that peripheral DCs and Langerhans cells are also not affected by Notch1 deficiency. Our results demonstrate that the development of DCs is totally independent of Notch1 function, and strongly suggest a dissociation between intrathymic T cell and DC precursors

Osteogenic Oxysterol, 20(S)-Hydroxycholesterol, Induces Notch Target Gene Expression in Bone Marrow Stromal Cells

We previously reported that specific oxysterols stimulate osteogenic differentiation of pluripotent bone marrow stromal cells (MSCs) through activation of hedgehog (Hh) signaling and may serve as potential future therapies for intervention in osteopenia and osteoporosis. In this study we report that the osteogenic oxysterol 20(S)-hydroxycholesterol (20S) induces the expression of genes associated with Notch signaling. Using M2-10B4 (M2) MSCs, we found that 20S significantly induced HES-1, HEY-1, and HEY-2 mRNA expression compared with untreated cells, with maximal induction after 48 hours, whereas the nonosteogenic oxysterols did not. Similar observations were made when M2 cells were treated with sonic hedgehog (Shh), and the specific Hh pathway inhibitor cyclopamine blocked 20S-induced Notch target gene expression. 20S did not induce Notch target genes in Smo−/− mouse embryonic fibroblasts, further confirming the role of Hh signaling in 20S-induced expression of Notch target genes. Despite the inability of liver X-receptor (LXR) synthetic ligand TO901317 to induce Notch target genes in M2 cells, LXR knockdown studies using siRNA showed inhibition of 20S-induced HEY-1 but not HES-1 expression, suggesting the partial role of LXR signaling in MSC responses to 20S. Moreover, 20S-induced Notch target gene expression was independent of canonical Notch signaling because neither 20S nor Shh induced CBF1 luciferase reporter activity or NICD protein accumulation in the nucleus, which are hallmarks of canonical Notch signaling activation. Finally, HES-1 and HEY-1 siRNA transfection significantly inhibited 20S-induced osteogenic genes, suggesting that the pro-osteogenic effects of 20S are regulated in part by HES-1 and HEY-1. © 2010 American Society for Bone and Mineral Researc

The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands

Mutations in the DSL (Delta, Serrate, Lag2) Notch (N) ligand Delta-like (Dll) 3 cause skeletal abnormalities in spondylocostal dysostosis, which is consistent with a critical role for N signaling during somitogenesis. Understanding how Dll3 functions is complicated by reports that DSL ligands both activate and inhibit N signaling. In contrast to other DSL ligands, we show that Dll3 does not activate N signaling in multiple assays. Consistent with these findings, Dll3 does not bind to cells expressing any of the four N receptors, and N1 does not bind Dll3-expressing cells. However, in a cell-autonomous manner, Dll3 suppressed N signaling, as was found for other DSL ligands. Therefore, Dll3 functions not as an activator as previously reported but rather as a dedicated inhibitor of N signaling. As an N antagonist, Dll3 promoted Xenopus laevis neurogenesis and inhibited glial differentiation of mouse neural progenitors. Finally, together with the modulator lunatic fringe, Dll3 altered N signaling levels that were induced by other DSL ligands

Insulin-like growth factor-I prevents caspase-mediated apoptosis in Schwann cells

Both neurons and glia succumb to programmed cell death (PCD) when deprived of growth factors at critical periods in development or following injury. Insulin-like growth factor-I (IGF-I) prevents apoptosis in neurons in vitro. To investigate whether IGF-I can protect Schwann cells (SC) from apoptosis, SC were harvested from postnatal day 3 rats and maintained in serum-containing media until confluency. When cells were switched to serum-free defined media (DM) for 12–72 h, they underwent PCD. Addition of insulin or IGF-I prevented apoptosis. Bisbenzamide staining revealed nuclear condensation and formation of apoptotic bodies in SC grown in DM alone, but SC grown in DM plus IGF-I had normal nuclear morphology. The phosphatidylinositol 3-kinase (PI 3-K) inhibitor LY294002 blocked IGF-I–mediated protection. Caspase-3 activity was rapidly activated upon serum withdrawal in SC, and the caspase inhibitor BAF blocked apoptosis. These results suggest that IGF-I rescues SC from apoptosis via PI 3-K signaling which is upstream from caspase activation. © 1999 John Wiley & Sons, Inc. J Neurobiol 41: 540–548, 1999Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34481/1/9_ftp.pd

Jagged1 in the portal vein mesenchyme regulates intrahepatic bile duct development: insights into Alagille syndrome

Mutations in the human Notch ligand jagged 1 (JAG1) result in a multi-system disorder called Alagille syndrome (AGS). AGS is chiefly characterized by a paucity of intrahepatic bile ducts (IHBD), but also includes cardiac, ocular, skeletal, craniofacial and renal defects. The disease penetration and severity of the affected organs can vary significantly and the molecular basis for this broad spectrum of pathology is unclear. Here, we report that Jag1 inactivation in the portal vein mesenchyme (PVM), but not in the endothelium of mice, leads to the hepatic defects associated with AGS. Loss of Jag1 expression in SM22α-positive cells of the PVM leads to defective bile duct development beyond the initial formation of the ductal plate. Cytokeratin 19-positive cells are detected surrounding the portal vein, yet they are unable to form biliary tubes, revealing an instructive role of the vasculature in liver development. These findings uncover the cellular basis for the defining feature of AGS, identify mesenchymal Jag1-dependent and -independent stages of duct development, and provide mechanistic information for the role of Jag1 in IHBD formation