- Browse by Date Submitted
Department of Dermatology Works
Permanent URI for this collection
Browse
Browsing Department of Dermatology Works by browse.metadata.dateaccessioned
Now showing 1 - 10 of 172
Results Per Page
Sort Options
Item Dilysine motifs in exon 2b of SMN protein mediate binding to the COPI vesicle protein α-COP and neurite outgrowth in a cell culture model of spinal muscular atrophy(Oxford Journals, 2013-10-15) Custer, Sara K.; Todd, Adrian G.; Singh, Natalia N.; Androphy, Elliot J.; Department of Dermatology, School of MedicineSpinal muscular atrophy (SMA) is a devastating neuromuscular disorder that stems from low levels of survival of motor neuron (SMN) protein. The processes that cause motor neurons and muscle cells to become dysfunctional are incompletely understood. We are interested in neuromuscular homeostasis and the stresses put upon that system by loss of SMN. We recently reported that α-COP, a member of the coatomer complex of coat protein I (COPI) vesicles, is an SMN-binding partner, implicating this protein complex in normal SMN function. To investigate the functional significance of the interaction between α-COP and SMN, we constructed an inducible NSC-34 cell culture system to model the consequences of SMN depletion and find that depletion of SMN protein results in shortened neurites. Heterologous expression of human SMN, and interestingly over-expression of α-COP, restores normal neurite length and morphology. Mutagenesis of the canonical COPI dilysine motifs in exon 2b results in failure to bind to α-COP and abrogates the ability of human SMN to restore neurite outgrowth in SMN-depleted motor neuron-like NSC-34 cells. We conclude that the interaction between SMN and α-COP serves an important function in the growth and maintenance of motor neuron processes and may play a significant role in the pathogenesis of SMA.Item The Reverse Galeal Hinge Flap: Another Valuable Technique in the Repair of Scalp Defects Extending to the Calvarium(Lippincott Williams & Wilkins, 2015-04) Lam, Thomas; Miletta, Nathanial R.; Bingham, Jonathan L.; Department of Dermatology, IU School of MedicineOver the last 30 years, the estimated incidence of nonmelanoma skin cancer (NMSC) has increased from 300,000 to greater than 2 million cases. Approximately 15% of these cancers occur on the scalp.1 Given the increasing incidence of NMSC and their predilection for the scalp, the demand for scalp repairs will continue to rise. It is important that the dermatologic surgeon is equipped to manage these cases, in particular defects that extend to the bone.The repair of large scalp defects extending to the calvarium is especially challenging for several reasons. The primary closure of any large scalp wound is complicated by the relative inelasticity of scalp tissue and the convexity of the scalp. Rotation flaps are the mainstay technique of re-approximating large scalp wounds but are often unable to completely close very large defects.2 Skin grafts can also be used to cover wounds primarily or in conjunction with other closure techniques.2 However, when scalp defects extend to the bone, the poor vascularity of the osseous tissue severely limits both skin grafting and xenografting. Various approaches to making exposed bone more suitable for grafting have been described in the recent literature, and these techniques and their limitations will be briefly discussed.3–5 The authors will also present two cases that outline a simple method of re-establishing a vascular bed on exposed bone using a reverse galeal hinge flap.Item Eruptive Disseminated Porokeratosis Associated with Corticosteroid-Induced Immunosuppression(Wiley, 2015-10) Bednarek, Robert; Ezra, Navid; Toubin, Yulianna; Linos, Konstantinos; Mousdicas, Nico; Department of Dermatology, IU School of MedicineEruptive disseminated porokeratosis (EDP) is a disease that presents clinically with sudden onset of erythematous papules and plaques, with a ridge-like border histologically represented by a cornoid lamella. We report a case of EDP occurring in a 39-year-old woman 3 days after completion of a 2-week course of oral corticosteroid therapy for an acute asthma exacerbation. The patient was treated with emollients and sun protection. Unlike the more chronic disseminated superficial (actinic) porokeratosis, EDP secondary to immunosuppression from corticosteroid therapy has very rarely been reported in the dermatological literature.Item Autophagy dysregulation in cell culture and animals models of Spinal Muscular Atrophy(Elsevier, 2014-07) Custer, Sara K.; Androphy, Elliot J.; Department of Dermatology, IU School of MedicineAbnormal autophagy has become a central thread linking neurodegenerative diseases, particularly of the motor neuron. One such disease is spinal muscular atrophy (SMA), a genetic neuromuscular disorder caused by mutations in the SMN1 gene resulting in low levels of Survival Motor Neuron (SMN) protein. Despite knowing the causal protein, the exact intracellular processes that are involved in the selective loss of motor neurons remains unclear. Autophagy induction can be helpful or harmful depending on the situation, and we sought to understand the state of the autophagic response in SMA. We show that cell culture and animal models demonstrate induction of autophagy accompanied by attenuated autophagic flux, resulting in the accumulation of autophagosomes and their associated cargo. Expression of the SMN-binding protein a-COP, a known modulator of autophagic flux, can ameliorate this autophagic traffic jam.Item Toxic interaction between Th2 cytokines and Staphylococcus aureus in atopic dermatitis(Nature Publishing Group, 2014-08) Travers, Jeffrey B.; Department of Dermatology, IU School of MedicinePatients with atopic dermatitis (AD) are commonly colonized/infected with Staphylococcus aureus, and this bacterium is known to worsen the dermatitis. In this issue, Brauweiler et al. demonstrate a newly discovered mechanism by which Th2 cytokines involved in AD augments the toxicity of the lytic staphylococcal protein alpha toxin. This review presents mechanisms by which Th2 cytokines may interact with S. aureus to the detriment of the dermatitis.Item Topical photodynamic therapy induces systemic immunosuppression via generation of platelet-activating factor receptor ligands(Nature Publishing Group, 2015-01) Ferracini, Matheus; Sahu, Ravi P.; Harrison, Kathleen A.; Waeiss, Robert A.; Murphy, Robert C.; Jancar, Sonia; Konger, Raymond L.; Travers, Jeffrey B.; Department of Dermatology, IU School of MedicineItem Primary Apocrine Adenocarcinoma of the Axilla(2015-05) Kathrotiya, Puja R.; Bridge, Andrew T.; Warren, Simon J.; Do, Ha; Klenk, Alison S.; Xu, Lisa Y.; Mathur, Anubhav N.; Department of Dermatology, IU School of MedicinePrimary apocrine adenocarcinoma (AA) is a rare malignant cutaneous neoplasm that typically arises in areas of high apocrine gland density such as the axillae and the anogenital region. Due to the nonspecific clinical manifestation of AA, the differential diagnosis may be broad. The rarity of this neoplasm has led to a relative lack of well-established histologic and immunohistochemical diagnostic criteria, further complicating the diagnosis of AA. We report the case of a 49-year-old man with primary AA of the left axilla and provide a review of the clinical and histologic findings, epidemiology, and treatment modalities of this rare cutaneous neoplasm.Item Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility(Nature Publishing Group, 2015-04-23) Yin, Xianyong; Low, Hui Qi; Wang, Ling; Li, Yonghong; Ellinghaus, Eva; Han, Jiali; Estivill, Xavier; Sun, Liangdan; Zuo, Xianbo; Shen, Changbing; Zhu, Caihong; Zhang, Anping; Sanchez, Fabio; Padyukov, Leonid; Catanese, Joseph J.; Krueger, Gerald G.; Duffin, Kristina Callis; Mucha, Sören; Weichenthal, Michael; Weidinger, Stephan; Lieb, Wolfgang; Foo, Jia Nee; Li, Yi; Sim, Karseng; Liany, Herty; Irwan, Ishak; Teo, Yikying; Theng, Colin T. S.; Gupta, Rashmi; Bowcock, Anne; De Jager, Philip L.; Qureshi, Abrar A.; de Bakker, Paul I. W.; Seielstad, Mark; Liao, Wilson; Ståhle, Mona; Franke, Andre; Zhang, Xuejun; Liu, Jianjun; Department of Dermatology, IU School of MedicinePsoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations.Item Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication(Elsevier, 2015-04) Kanginakudru, Sriramana; DeSmet, Marsha; Thomas, Yanique; Morgan, Iain M.; Androphy, Elliot J.; Department of Dermatology, IU School of MedicineThe evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reduced viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number.Item Translational Repression Protects Human Keratinocytes from UVB-Induced Apoptosis through a Discordant eIF2 Kinase Stress Response(Nature Publishing Group, 2015-10) Collier, Ann E.; Wek, Ronald C.; Spandau, Dan F.; Department of Dermatology, IU School of MedicineThis study delineates the mechanisms by which UVB regulates protein synthesis in human keratinocytes and the importance of translational control in cell survival. Translation initiation is regulated by phosphorylation of eukaryotic initiation factor 2 (eIF2-P) that causes decreased global protein synthesis coincident with enhanced translation of selected stress-related transcripts, such as activating transcription factor 4 (ATF4). ATF4 is a transcriptional activator of the integrated stress response (ISR) that has cytoprotective functions as well as apoptotic signals through the downstream transcriptional regulator C/EBP homologous protein (CHOP; GADD153/DDIT3). We determined that UVB irradiation is a potent inducer of eIF2-P in keratinocytes, leading to decreased levels of translation initiation. However, expression of ATF4 or CHOP was not induced by UVB as compared with traditional ISR activators. The rationale for this discordant response is that ATF4 mRNA is reduced by UVB, and despite its ability to be preferentially translated, there are diminished levels of available transcript. Forced expression of ATF4 and CHOP protein before UVB irradiation significantly enhanced apoptosis, suggesting that this portion of the ISR is deleterious in keratinocytes following UVB. Inhibition of eIF2-P and translational control reduced viability following UVB that was alleviated by cycloheximide (CHX), indicating that translation repression through eIF2-P is central to keratinocyte survival.