http://hdl.handle.net/10027/7299 Sat, 18 May 2013 08:40:07 GMT 2013-05-18T08:40:07Z http://hdl.handle.net/10027/9641 Early, nonciliary role for microtubule proteins in left-right patterning is conserved across kingdoms Lobikin, Maria; Wang, Gang; Xu, Jing-Song; Hsieh, Yi-Wen; Chuang, Chiou-Fen; Lemire, Joan M.; Levin, Michael Many types of embryos’ bodyplans exhibit consistently-oriented laterality of the heart, viscera, and brain. Errors of left-right patterning present an important class of human birth defects, and considerable controversy exists about the nature and evolutionary conservation of the molecular mechanisms that allow embryos to reliably orient the left-right axis. Here we show that the same mutations in the cytoskeletal protein tubulin that alter asymmetry in plants also affect very early steps of left-right patterning in nematode and frog embryos, as well as chirality of human cells in culture. In the frog embryo, tubulin α and tubulin γ-associated protein are required for the differential distribution of maternal proteins to the left or right blastomere at the first cell division. Our data reveal a remarkable molecular conservation of mechanisms initiating left-right asymmetry. The origin of laterality is cytoplasmic, ancient, and highly conserved across kingdoms – a fundamental feature of the cytoskeleton that underlies chirality in cells and multicellular organisms. This is a copy of an article published in the Proceedings of the National Academy of Sciences © 2012 National Academy of Sciences. The final publication is available at www.pnas.org/ doi: 10.1073/pnas.1202659109 Tue, 31 Jul 2012 05:00:00 GMT http://hdl.handle.net/10027/9641 2012-07-31T05:00:00Z http://hdl.handle.net/10027/8722 Assessing students' ability to detect melanomas using standardized patients and moulage Hernandez, Claudia; Mermelstein, Robin; Robinson, June K.; Yudkowsky, Rachel Detection of melanoma by physicians via opportunistic surveillance during focused physical examinations may reduce mortality. Medical students may not encounter a clinical case of melanoma during a dermatology clerkship. NOTICE: this is the author’s version of a work that was accepted for publication in Journal of The American Academy of Dermatology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of The American Academy of Dermatology, 2011 Dec. DOI:10.1016/j.jaad.2011.10.032 Thu, 01 Dec 2011 06:00:00 GMT http://hdl.handle.net/10027/8722 2011-12-01T06:00:00Z http://hdl.handle.net/10027/8528 IL-4 Regulates Chemokine CCL26 in Keratinocytes through the Jak1, 2/Stat6 Signal Transduction Pathway: Implication for Atopic Dermatitis Bao, Lei; Shi, Vivian Y.; Chan, Lawrence S. Atopic dermatitis (AD), a chronic, pruritic, inflammatory skin disease, is histopathologically characterized by epidermal hyperplasia and infiltration of T cells, mast cells, and eosinophils. Clinical study and basic research have established that IL-4 plays an important role in the pathogenesis of AD. In this report, using HaCat cells, we show that CCL26, a chemokine for eosinophils, is up-regulated by IL-4 at both the mRNA and protein levels. IL-4 also enhances CCL26 promoter activity. Serial 5’ deletion of the promoter and mutagenesis study reveal that the proximal Stat site is the key response element for IL-4 regulation of CCL26. Although IL-4 increases phosphorylation of both Stat3 and Stat6, it only activates Stat6 as shown by dominant negative studies. In addition, we found that IL-4 induces Stat6 nuclear translocation and stimulates phosphorylation of Jak1 and Jak2 but not Tyk2. IL-4 up-regulation of CCL26 can be suppressed by Jak inhibitors in a dose-dependent manner. Taken together, results of this investigation reveal that IL-4 signals through the Jak1, 2/Stat6 pathway in keratinoctyes to stimulate CCL26 expression and this may provide an explanation for the pathogenesis of AD. NOTICE: this is the author’s version of a work that was accepted for publication in Molecular Immunology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Molecular Immunology, [Vol 50, Issue 1-2, Feb 2012. DOI: 10.1016/j.molimm.2011.12.008 Wed, 01 Feb 2012 06:00:00 GMT http://hdl.handle.net/10027/8528 2012-02-01T06:00:00Z http://hdl.handle.net/10027/8518 Ocular and Oral Mucous Membrane Pemphigoid (Cicatricial Pemphigoid) Chan, Lawrence S. Mucous membrane pemphigoid, a heterogeneous group of autoimmune blistering diseases, affect primarily the mucous membranes. While both oral and ocular mucosae can be affected in a given patient, patients have involvement restricted to oral mucosae tend to have a benign outcome, whereas those with ocular disease commonly face treatment resistance and result in scarring and blindness. Diagnosis requires a direct immunofluorescence microscopy demonstrating a linear deposition of IgG, IgA, or C3 at the epithelial basement membrane. While the target antigens vary, subsets of patients affected exclusively by oral and ocular mucosal diseases have autoantibodies targeting alpha‐6 and beta‐4 integrins, respectively. NOTICE: this is the author’s version of a work that was accepted for publication in Clinics in Dermatology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Clinics in Dermatology, Vol 30, Issue 1, Jan/Feb 2012. DOI: 10.1016/j.clindermatol.2011.03.007 Sun, 01 Jan 2012 06:00:00 GMT http://hdl.handle.net/10027/8518 2012-01-01T06:00:00Z