Aminoacyl tRNA synthetase complex interacting multifunctional protein 1 simultaneously binds Glutamyl-Prolyl-tRNA synthetase and scaffold protein aminoacyl tRNA synthetase complex interacting multifunctional protein 3 of the multi-tRNA synthetase complex

Higher eukaryotes have developed extensive compartmentalization of amino acid (aa) - tRNA coupling through the formation of a multi-synthetase complex (MSC) that is composed of eight aa-tRNA synthetases (ARS) and three scaffold proteins: aminoacyl tRNA synthetase complex interacting multifunctional proteins (AIMP1, 2 and 3). Lower eukaryotes have a much smaller complex while yeast MSC consists of only two ARS (MetRS and GluRS) and one ARS cofactor 1 protein, Arc1p (Simos et al., 1996), the homolog of the mammalian AIMP1. Arc1p is reported to form a tripartite complex with GluRS and MetRS through association of the N-terminus GST-like domains (GST-L) of the three proteins (Koehler et al., 2013). Mammalian AIMP1 has no GST-L domain corresponding to Arc1p N-terminus. Instead, AIMP3, another scaffold protein of 18 kDa composed entirely of a GST-L domain, interacts with Methionyl-tRNA synthetase (MARS) (Quevillon et al., 1999) and Glutamyl-Prolyl-tRNA Synthetase (EPRS) (Cho et al., 2015). Here we report two new interactions between MSC members: AIMP1 binds to EPRS and AIMP1 binds to AIMP3. Interestingly, the interaction between AIMP1 and AIMP3 complex makes it the functional equivalent of a single Arc1p polypeptide in yeast. This interaction is not mapped to AIMP1 N-terminal coiled-coil domain, but rather requires an intact tertiary structure of the entire protein. Since AIMP1 also interacts with AIMP2, all three proteins appear to compose a core docking structure for the eight ARS in the MSC complex

A rural undergraduate campus in England:virtue from opportunity and necessity

The implementation of new curriculum at Keele University Medical School, UK has made heavy use of general practice as a locus for learning. This has necessitated a substantial expansion in the School's teaching network. The School's hinterland includes a large rural area with a number of excellent general practices and associated community hospitals that, to date, have been unable to teach undergraduates because of their inaccessibility. This article describes how the School and its partners articulated a vision to establish a rural campus with an associated rural accommodation hub, and the challenges involved in establishing and sustaining the campus

Introduction: On Connection, Diversity, and Resilience in Writing Across the Curriculum

Developed from presentations at the 2018 International Writing Across the Curriculum conference, this collection documents a key moment in the history of WAC, foregrounding connection and diversity as keys to the sustainability of the WAC movement in the face of new and long-standing challenges. Contributors reflect on the history and ongoing evolution of WAC, honoring grassroots efforts while establishing a more unified structure of collaborative leadership and mentorship. The chapters in this collection offer a rich variety of practices, pedagogies, mindsets, and methodologies for readers who are invested in using writing in a wide range of institutional and disciplinary contexts. Boldly engaging such pressing topics as translingualism, anti-racism, emotional labor, and learning analytics, the 18 chapters collected here testify to WAC\u27s durability, persistence, and resilience in an ever-changing educational landscape

A LIGHT AND ELECTRON MICROSCOPE STUDY OF LONG-TERM ORGANIZED CULTURES OF RAT DORSAL ROOT GANGLIA

Dorsal root ganglia from fetal rats were explanted on collagen-coated coverslips and carried in Maximow double-coverslip assemblies for periods up to 3 months. These cultured ganglia were studied in the living state, in stained whole mounts, and in sections after OsO4 fixation and Epon embedment. From the central cluster of nerve cell bodies, neurites emerge to form a rich network of fascicles which often reach the edge of the carrying coverslip. The neurons resemble their in vivo counterparts in nuclear and cytoplasmic content and organization; e.g., they appear as "light" or "dark" cells, depending on the amount of cytoplasmic neurofilaments. Satellite cells form a complete investment around the neuronal soma and are themselves everywhere covered by basement membrane. The neuron-satellite cell boundary is complicated by spinelike processes arising from the neuronal soma. Neuron size, myelinated fiber diameter, and internode length in the cultures do not reach the larger of the values known for ganglion and peripheral nerve in situ (30). Unmyelinated and myelinated nerve fibers and associated Schwann cells and endoneurial and perineurial components are organized into typical fascicles. The relationship of the Schwann cell and its single myelinated fiber or numerous unmyelinated fibers and the properties of myelin, such as lamellar spacing, mesaxons, Schmidt-Lanterman clefts, nodes of Ranvier, and protuberances, mimic the in vivo pattern. It is concluded that cultivation of fetal rat dorsal root ganglia by this technique fosters maturation and long-term maintenance of all the elements that comprise this cellular community in vivo (except vascular components) and, furthermore, allows these various components to relate faithfully to one another to produce an organotypic model of sensory ganglion tissue

The Mixed Methods Appraisal Tool (MMAT) version 2018 for information professionals and researchers

INTRODUCTION: Appraising the quality of studies included in systematic reviews combining qualitative and quantitative evidence is challenging. To address this challenge, a critical appraisal tool was developed: the Mixed Methods Appraisal Tool (MMAT). The aim of this paper is to present the enhancements made to the MMAT. DEVELOPMENT: The MMAT was initially developed in 2006 based on a literature review on systematic reviews combining qualitative and quantitative evidence. It was subject to pilot and interrater reliability testing. A revised version of the MMAT was developed in 2018 based on the results from usefulness testing, a literature review on critical appraisal tools and a modified e-Delphi study with methodological experts to identify core criteria. TOOL DESCRIPTION: The MMAT assesses the quality of qualitative, quantitative, and mixed methods studies. It focuses on methodological criteria and includes five core quality criteria for each of the following five categories of study designs: (a) qualitative, (b) randomized controlled, (c) nonrandomized, (d) quantitative descriptive, and (e) mixed methods. CONCLUSION: The MMAT is a unique tool that can be used to appraise the quality of different study designs. Also, by limiting to core criteria, the MMAT can provide a more efficient appraisal

Epigenetic regulator MLL2 shows altered expression in cancer cell lines and tumors from human breast and colon

<p>Abstract</p> <p>Background</p> <p>MLL2, an epigenetic regulator in mammalian cells, mediates histone 3 lysine 4 tri-methylation (H3K4me3) through the formation of a multiprotein complex. MLL2 shares a high degree of structural similarity with MLL, which is frequently disrupted in leukemias via chromosomal translocations. However, this structural similarity is not accompanied by functional equivalence. In light of this difference, and previous reports on involvement of epigenetic regulators in malignancies, we investigated MLL2 expression in established cell lines from breast and colon tissues. We then investigated MLL2 in solid tumors of breast and colon by immunohistochemistry, and evaluated potential associations with established clinicopathologic variables.</p> <p>Results</p> <p>We examined MLL2 at both transcript and protein levels in established cell lines from breast and colon cancers. Examination of these cell lines showed elevated levels of MLL2. Furthermore, we also identified incomplete proteolytic cleavage of MLL2 in the highly invasive tumor cell lines. To corroborate these results, we studied tumor tissues from patients by immunohistochemistry. Patient samples also revealed increased levels of MLL2 protein in invasive carcinomas of the breast and colon. In breast, cytoplasmic MLL2 was significantly increased in tumor tissues compared to adjacent benign epithelium (p < 0.05), and in colon, both nuclear and cytoplasmic immunostaining was significantly increased in tumor tissues compared to adjacent benign mucosa (p < 0.05).</p> <p>Conclusion</p> <p>Our study indicates that elevated levels of MLL2 in the breast and colon cells are associated with malignancy in these tissues, in contrast to MLL involvement in haematopoietic cancer. In addition, both abnormal cellular localization of MLL2 and incomplete proteolytic processing may be associated with tumor growth/progression in breast and colonic tissues. This involvement of MLL2 in malignancy may be another example of the role of epigenetic regulators in cancer.</p