Medical Sciences Commons^™

Effects Of Hypothyroidism On Cell Proliferation And Neuroblasts In The Hippocampal Dentate Gyrus In A Rat Model Of Type 2 Diabetes, Sun Shin Yi, In Koo Hwang, Ji Won Choi, Moo-Ho Won, Je Kyung Seong, Yeo Sung Yoon

Biomedical Sciences Faculty Research and Publications

We observed how the hypothyroid state affects diabetic states and modifies cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG). For this, 0.03% methimazole, an anti-thyroid drug, was administered to 7-week-old, pre-diabetic Zucker diabetic fatty (ZDF) rats by drinking water for 5 weeks, and the animals were sacrificed at 12 weeks of age. At this age, corticosterone levels were significantly increased in the ZDF rats compared to those in the control (Zucker lean control, ZLC) rats. Methimazole (methi) treatment in the ZDF rats (ZDF-methi rats) significantly decreased corticosterone levels and diabetes-induced hypertrophy of adrenal glands. In the DG, …

Molecular Requirements For Ethanol Differential Allosteric Modulation Of Ligand-Gated Ion Channels Based On Selective Gβγ Modulation, Gonzalo E. Yevenes, Gustavo Moraga-Cid, Ariel Avila, Leonardo Guzman, Maximiliano Figueroa, Robert W. Peoples, Luis G. Aguayo

Biomedical Sciences Faculty Research and Publications

It is now believed that the allosteric modulation produced by ethanol in glycine receptors (GlyRs) depends on alcohol binding to discrete sites within the protein structure. Thus, the differential ethanol sensitivity of diverse GlyR isoforms and mutants was explained by the presence of specific residues in putative alcohol pockets. Here, we demonstrate that ethanol sensitivity in two LGIC members, the GlyR adult α₁ and embryonic α₂ subunits, can be modified through selective mutations that rescued or impaired Gβγ modulation. Even though that both isoforms were able to physically interact with Gβγ, only the α₁ GlyR was functionally …

Ranolazine Is Effective For Acute Or Chronic Ischemic Dysfunction With Heart Failure, Sudip Nanda Md, Facp, Matthew W. Martinez Md, Tanujit Dey Phd

Department of Medicine

No abstract provided.

Transcriptional Profiles For Glutamate Transporters Reveal Differences Between Organophosphates But Similarities With Unrelated Neurotoxicants, Theodore A. Slotkin, Doug Lobner, Frederic J. Seidler

Biomedical Sciences Faculty Research and Publications

The developmental neurotoxicity of organophosphates involves mechanisms other than their shared property as cholinesterase inhibitors, among which are excitotoxicity and oxidative stress. We used PC12 cells as a neurodevelopmental model to compare the effects of chlorpyrifos and diazinon on the expression of genes encoding glutamate transporters. Chlorpyrifos had a greater effect in cells undergoing nerve growth factor-induced neurodifferentiation as compared to undifferentiated PC12 cells, with peak sensitivity at the initiation of differentiation, reflecting a global upregulation of all the glutamate transporter genes expressed in this cell line. In differentiating cells, chlorpyrifos had a significantly greater effect than did diazinon and …

Survival Associated Pathway Identification With Group Lp Penalized Global Auc Maximization., Zhenqiu Liu, Laurence S Magder, Terry Hyslop, Li Mao

Department of Pharmacology and Experimental Therapeutics Faculty Papers

It has been demonstrated that genes in a cell do not act independently. They interact with one another to complete certain biological processes or to implement certain molecular functions. How to incorporate biological pathways or functional groups into the model and identify survival associated gene pathways is still a challenging problem. In this paper, we propose a novel iterative gradient based method for survival analysis with group Lp penalized global AUC summary maximization. Unlike LASSO, Lp (p < 1) (with its special implementation entitled adaptive LASSO) is asymptotic unbiased and has oracle properties 1. We first extend Lp for individual gene identification to group Lp penalty for pathway selection, and then develop a novel iterative gradient algorithm for penalized global AUC summary maximization (IGGAUCS). This method incorporates the genetic pathways into global AUC summary maximization and identifies survival associated pathways instead of individual genes. The tuning parameters are determined using 10-fold cross validation with training data only. The prediction performance is evaluated using test data. We apply the proposed method to survival outcome analysis with gene expression profile and identify multiple pathways simultaneously. Experimental results with simulation and gene expression data demonstrate that the proposed procedures can be used for identifying important biological pathways that are related to survival phenotype and for building a parsimonious model for predicting the survival times.

Cortisol Exerts Bi-Phasic Regulation Of Inflammation In Humans, Mark P. Yeager, Patricia Pioli, Paul M. Guyre

Dartmouth Scholarship

Natural and synthetic glucocorticoids (GCs) have been used for decades to suppress inflammation. In this paper, we re-examine the role of the endogenous GC, cortisol, as a primary homeostatic regulator of the human inflammatory response to injury. Our data show that cortisol regulation of innate immunity can be both pro-inflammatory and anti-inflammatory. Using a human model of in vivo cortisol depletion, we first show that baseline (diurnal) cortisol concentrations do not exert an anti-inflammatory effect. This is the first clue that cortisol regulation of inflammation is not represented by a linear dose-response relationship. We next show in surgical patients that …

Acaricidal Activity Of Eugenol Based Compounds Against Scabies Mites, Cielo Pasay, Kate Mounsey, Graeme Stevenson, Rohan Davis, Larry G. Arlian, Marjorie Morgan, Diann Vyszenski-Moher, Kathy Andrews, James Mccarthy

Biological Sciences Faculty Publications

Background

Human scabies is a debilitating skin disease caused by the “itch mite” Sarcoptes scabiei. Ordinary scabies is commonly treated with topical creams such as permethrin, while crusted scabies is treated with topical creams in combination with oral ivermectin. Recent reports of acaricide tolerance in scabies endemic communities in Northern Australia have prompted efforts to better understand resistance mechanisms and to identify potential new acaricides. In this study, we screened three essential oils and four pure compounds based on eugenol for acaricidal properties.

Methodology/Principal Findings

Primary Human Mammary Epithelial Cells Endocytose Hiv-1 And Facilitate Viral Infection Of Cd4+ T Lymphocytes, Stephanie M. Dorosko, Ruth I. Connor

Dartmouth Scholarship

The contribution of mammary epithelial cells (MEC) to human immunodeficiency virus type 1 (HIV-1) in breast milk remains largely unknown. While breast milk contains CD4(+) cells throughout the breast-feeding period, it is not known whether MEC directly support HIV-1 infection or facilitate infection of CD4(+) cells in the breast compartment. This study evaluated primary human MEC for direct infection with HIV-1 and for indirect transfer of infection to CD4(+) target cells. Primary human MEC were isolated and assessed for expression of HIV-1 receptors. MEC were exposed to CCR5-, CXCR4- and dual-tropic strains of HIV-1 and evaluated for viral reverse transcription …

Radially Aligned, Electrospun Nanofibers As Dural Substitutes For Wound Closure And Tissue Regeneration Applications, Jingwei Xie, Matthew R. Macewan, Wilson Z. Ray, Wenying Liu, Daku Y. Siewe, Younan Xia

MIIR Faculty Research

This paper reports the fabrication of scaffolds consisting of radially aligned poly(ε-caprolactone) nanofibers by utilizing a collector composed of a central point electrode and a peripheral ring electrode. This novel class of scaffolds was able to present nanoscale topographic cues to cultured cells, directing and enhancing their migration from the periphery to the center. We also established that such scaffolds could induce faster cellular migration and population than nonwoven mats consisting of random nanofibers. Dural fibroblast cells cultured on these two types of scaffolds were found to express type I collagen, the main extracellular matrix component in dural mater. The …

Formation Of Complex And Unstable Chromosomal Translocations In Yeast, Kristina H. Schmidt, Emilie Viebranz, Lillian Doerfler, Christina Lester, Aaron Rubenstein

Molecular Biosciences Faculty Publications

Genome instability, associated with chromosome breakage syndromes and most human cancers, is still poorly understood. In the yeast Saccharomyces cerevisiae, numerous genes with roles in the preservation of genome integrity have been identified. DNA-damage-checkpoint-deficient yeast cells that lack Sgs1, a RecQ-like DNA helicase related to the human Bloom's-syndrome-associated helicase BLM, show an increased rate of genome instability, and we have previously shown that they accumulate recurring chromosomal translocations between three similar genes, CAN1, LYP1 and ALP1. Here, the chromosomal location, copy number and sequence similarity of the translocation targets ALP1 and LYP1 were altered to gain insight into the …

The Staphylococcus-Specific Gene Rsr Represses Agr And Virulence In Staphylococcus Aureus, Sandeep Tamber, Dindo Reyes, Niles P. Donegan, Joseph D. Schwartzman, Ambrose L. Cheung, Guido Memmi

Dartmouth Scholarship

The expression of virulence factors in Staphylococcus aureus is tightly coordinated by a vast network of regulatory molecules. In this report, we characterize a genetic locus unique to staphylococci called rsr that has a role in repressing two key virulence regulators, sarR and agr. Using strain SH1000, we showed that the transcription of virulence effectors, such as hla, sspA, and spa, is altered in an rsr mutant in a way consistent with agr upregulation. Analysis of RNAIII expression of the agr locus in rsr and rsr-sarR mutants indicated that rsr likely contributes to agr expression independently …

S-Glutathionylation Activates Stim1 And Alters Mitochondrial Homeostasis., Brian J Hawkins, Krishna M Irrinki, Karthik Mallilankaraman, Yu-Chin Lien, Youjun Wang, Cunnigaiper D Bhanumathy, Ramasamy Subbiah, Michael F Ritchie, Jonathan Soboloff, Yoshihiro Baba, Tomohiro Kurosaki, Suresh K Joseph, Donald L Gill, Muniswamy Madesh

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Oxidant stress influences many cellular processes, including cell growth, differentiation, and cell death. A well-recognized link between these processes and oxidant stress is via alterations in Ca(2+) signaling. However, precisely how oxidants influence Ca(2+) signaling remains unclear. Oxidant stress led to a phenotypic shift in Ca(2+) mobilization from an oscillatory to a sustained elevated pattern via calcium release-activated calcium (CRAC)-mediated capacitive Ca(2+) entry, and stromal interaction molecule 1 (STIM1)- and Orai1-deficient cells are resistant to oxidant stress. Functionally, oxidant-induced Ca(2+) entry alters mitochondrial Ca(2+) handling and bioenergetics and triggers cell death. STIM1 is S-glutathionylated at cysteine 56 in response to …

Harnessing The Effect Of Adoptively Transferred Tumor-Reactive T Cells On Endogenous (Host-Derived) Antitumor Immunity, Yolanda Nesbeth, Jose R. Conejo-Garcia

Dartmouth Scholarship

Adoptive T cell transfer therapy, the ex vivo activation, expansion, and subsequent administration of tumor-reactive T cells, is already the most effective therapy against certain types of cancer. However, recent evidence in animal models and clinical trials suggests that host conditioning interventions tailored for some of the most aggressive and frequent epithelial cancers will be needed to maximize the benefit of this approach. Similarly, the subsets, stage of differentiation, and ex vivo expansion procedure of tumor-reactive T cells to be adoptively transferred influence their in vivo effectiveness and may need to be adapted for different types of cancer and host …

Cannabinoid Receptors In The 3d Reconstructed Mouse Brain: Function And Regulation, Peter Nguyen

Theses and Dissertations

CB1 receptors (CB1R) mediate the psychoactive and therapeutic effects of cannabinoids including ∆9-tetrahydrocannabinol (THC), the main psychoactive constituent in marijuana. However, therapeutic use is limited by side effects and tolerance and dependence with chronic administration. Tolerance to cannabinoid-mediated effects is associated with CB1R adaptations, including desensitization (receptor-G-protein uncoupling) and downregulation (receptor degradation). The objectives of this thesis are to investigate the regional-specificity in CB1R function and regulation. Previous studies have investigated CB1Rs in a subset of regions involved in cannabinoid effects, but an inclusive regional comparison of the relative efficacies of different classes of cannabinoids to activate G-proteins has not …

Psychometric Properties Of Three Instruments To Measure Fatigue With Myocardial Infarction, Ann Eckhardt, Anne Fink, Michelle Fennessy, Jessica Jones, Donna Kruse, Kathryn Vanderzwan, Catherine Ryan, Julie Zerwic

Scholarship

The purpose of this study was to evaluate the psychometric properties of three questionnaires to measure fatigue with myocardial infarction. The Fatigue Symptom Inventory Interference Scale, Profile of Moods States Fatigue subscale (POMS-F), and Short Form 36 (SF-36) Vitality Scale were completed during hospitalization (n = 116) and 30 days after hospital admission (n = 49). Moderate to strong correlations were found among each of these fatigue scales and between each fatigue scale and measures of other variables to include vigor, depressed mood, anxiety, and physical functioning. POMS-F scores decreased significantly at Time 2, but this decline in …

Cord Blood Versus Age 5 Mononuclear Cell Proliferation On Ige And Asthma, Carolyn Chang, Kevin Gauvey-Kern, Alina Johnson, Elizabeth A. Kelvin, Ginger L. Chew, Frederica Perera, Rachel L. Miller

Publications and Research

Background: Fetal immune responses following exposure of mothers to allergens during pregnancy may influence the subsequent risk of childhood asthma. However, the association of allergen-induced cord blood mononuclear cell (CBMC) proliferation and cytokine production with later allergic immune responses and asthma has been controversial. Our objective was to compare indoor allergen-induced CBMC with age 5 peripheral blood mononuclear cell (PBMC) proliferation and determine which may be associated with age 5 allergic immune responses and asthma in an inner city cohort.

Methods: As part of an ongoing cohort study of the Columbia Center for Children’s Environmental Health (CCCEH), CBMCs and age …

Mononucleosis And Antigen-Driven T Cell Responses Have Different Requirements For Interleukin-2 Signaling In Murine Gammaherpesvirus Infection, Michael Molloy, Weijun Zhang, Edward Usherwood

Dartmouth Scholarship

Interleukin-2 (IL-2) has been implicated as being necessary for the optimal formation of primary CD8⁺ T cell responses against various pathogens. Here we have examined the role that IL-2 signaling plays in several aspects of a CD8⁺ T cell response against murine gammaherpesvirus 68 (MHV-68). Exposure to MHV-68 causes a persistent infection, along with infectious mononucleosis, providing a model for studying these processes in mice. Our study indicates that CD25 is necessary for optimal expansion of the antigen-specific CD8⁺ T cell response but not for the long-term memory response. Contrastingly, IL-2 signaling through CD25 is absolutely required …

Cross-Reactivity Of Antibodies Against Leptospiral Recurrent Uveitis-Associated Proteins A And B (Lrua And Lrub) With Eye Proteins, Ashutosh Verma, Pawan Kumar, Kelly Babb, John F. Timoney, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Infection by Leptospira interrogans has been causally associated with human and equine uveitis. Studies in our laboratories have demonstrated that leptospiral lipoprotein LruA and LruB are expressed in the eyes of uveitic horses, and that antibodies directed against LruA and LruB react with equine lenticular and retinal extracts, respectively. These reactivities were investigated further by performing immunofluorescent assays on lenticular and retinal tissue sections. Incubation of lens tissue sections with LruA-antiserum and retinal sections with LruB-antiserum resulted in positive fluorescence. By employing two-dimensional gel analyses followed by immunoblotting and mass spectrometry, lens proteins cross-reacting with LruA antiserum were identified to …

A Coupled Finite Element-Boundary Element Method For Modeling Diffusion Equation In 3d Multi-Modality Optical Imaging, Subhadra Srinivasan, Hamid R. Ghadyani, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

Three dimensional image reconstruction for multi-modality optical spectroscopy systems needs computationally efficient forward solvers with minimum meshing complexity, while allowing the flexibility to apply spatial constraints. Existing models based on the finite element method (FEM) require full 3D volume meshing to incorporate constraints related to anatomical structure via techniques such as regularization. Alternate approaches such as the boundary element method (BEM) require only surface discretization but assume homogeneous or piece-wise constant domains that can be limiting. Here, a coupled finite element-boundary element method (coupled FE-BEM) approach is demonstrated for modeling light diffusion in 3D, which uses surfaces to model exterior …

Age, Reproduction, Growth, Condition And Diet Of The Introduced Yellow Bass, Morone Mississippiensis, In Barren River Lake, Kentucky, Peter Zervas

Masters Theses & Specialist Projects

Introduction of fish species to North American drainages has occurred for over 100 years. Introduced fish species have been documented to have adverse effects on both the environment and native species of the drainage into which they have been introduced. To better understand the effects that introduced species may have on a particular drainage, it is essential to understand aspects of the introduced species' life history. The objectives of the current study is to quantify the age, reproduction, growth, condition and diet of the yellow bass, Morone mississippiensis, in Barren River Lake, Kentucky. Monthly collections from three areas on Barren …

Hyperpolarized (3)He Magnetic Resonance Imaging-Derived Pulmonary Pressure-Volume Curves, Stephen Choy, Andrew Wheatley, David G Mccormack, Grace Parraga

Medical Biophysics Publications

We aimed to evaluate the potential for the use of hyperpolarized helium-3 magnetic resonance imaging (MRI) apparent diffusion coefficient (ADC) surrogates of alveolar size, together with literature-based morphological parameters in a theoretical model of lung mechanics to simulate noninvasive transpulmonary pressure-volume curves. Fourteen ex-smokers with chronic obstructive pulmonary disease (COPD) (n = 8 stage II, n = 6 stage III/IV COPD) and five age-matched never-smokers, provided written, informed consent and were evaluated at baseline and 26 + or - 2 mo later (n = 15 subjects) using plethysmography, spirometry, and (3)He MRI at 3.0 T. Total lung capacity, residual volume, …

Neural Reuse: A Fundamental Organizational Principle Of The Brain, Michael Anderson

Brain and Mind Institute Researchers' Publications

An emerging class of theories concerning the functional structure of the brain takes the reuse of neural circuitry for various cognitive purposes to be a central organizational principle. According to these theories, it is quite common for neural circuits established for one purpose to be exapted (exploited, recycled, redeployed) during evolution or normal development, and be put to different uses, often without losing their original functions. Neural reuse theories thus differ from the usual understanding of the role of neural plasticity (which is, after all, a kind of reuse) in brain organization along the following lines: According to neural reuse, …

Evaluation Of The Quantitative Accuracy Of A Commercially-Available Positron Emission Mammography Scanner, Adam Springer

Dissertations and Theses (Open Access)

Objective: The PEM Flex Solo II (Naviscan, Inc., San Diego, CA) is currently the only commercially-available positron emission mammography (PEM) scanner. This scanner does not apply corrections for count rate effects, attenuation or scatter during image reconstruction, potentially affecting the quantitative accuracy of images. This work measures the overall quantitative accuracy of the PEM Flex system, and determines the contributions of error due to count rate effects, attenuation and scatter.

Materials and Methods: Gelatin phantoms were designed to simulate breasts of different sizes (4 – 12 cm thick) with varying uniform background activity concentration (0.007 – 0.5 μCi/cc), cysts and …

Defining The Role Of Il-15 Trans-Presentation By Distinct Cell-Types During The Development And Homeostasis Of Natural Killer And Invariant Natural Killer T Cells, Eliseo F. Castillo

Dissertations and Theses (Open Access)

The immuno-regulatory functions displayed by NK and iNKT cells have highlighted their importance as key lymphocytes involved in innate and adaptive immunity. Therefore, understanding the dynamics influencing the generation of NK and iNKT cells is extremely important. IL-15 has been shown to provide a critical signal throughout the development and homeostasis of NK and iNKT cells; however, the cellular source of IL-15 has remained unclear. In this investigation, I provide evidence that the cell-type providing IL-15 to NK and iNKT cells via trans-presentation is determined by the tissue site and the maturation status of NK and iNKT cells. For NK …

Thoracic Target Volume Delineation Using Various Maximum-Intensity Projection Computed To Mography Image Sets For Stereotactic Body Radiation Therapy, David A. Zamora

Dissertations and Theses (Open Access)

The motion of lung tumors during respiration makes the accurate delivery of radiation therapy to the thorax difficult because it increases the uncertainty of target position. The adoption of four-dimensional computed tomography (4D-CT) has allowed us to determine how a tumor moves with respiration for each individual patient. Using information acquired during a 4D-CT scan, we can define the target, visualize motion, and calculate dose during the planning phase of the radiotherapy process. One image data set that can be created from the 4D-CT acquisition is the maximum-intensity projection (MIP). The MIP can be used as a starting point to …

The Catalytic Function Of The Rev1 Dcmp Transferase Is Required In A Lesion-Specific Manner For Translesion Synthesis And Base Damage-Induced Mutagenesis, Ying Zhou, Jillian Wang, Yanbin Zhang, Zhigang Wang

Toxicology and Cancer Biology Faculty Publications

The Rev1-Polζ pathway is believed to be the major mechanism of translesion DNA synthesis and base damage-induced mutagenesis in eukaryotes. While it is widely believed that Rev1 plays a non-catalytic function in translesion synthesis, the role of its dCMP transferase activity remains uncertain. To determine the relevance of its catalytic function in translesion synthesis, we separated the Rev1 dCMP transferase activity from its non-catalytic function in yeast. This was achieved by mutating two conserved amino acid residues in the catalytic domain of Rev1, i.e. D467A/E468A, where its catalytic function was abolished but its non-catalytic function remained intact. In this mutant …

Improving Quantitative Treatment Response Monitoring With Deformable Image Registration, Blake A. Cannon

Dissertations and Theses (Open Access)

Quantitative imaging with 18F-FDG PET/CT has the potential to provide an in vivo assessment of response to radiotherapy (RT). However, comparing tissue tracer uptake in longitudinal studies is often confounded by variations in patient setup and potential treatment induced gross anatomic changes. These variations make true response monitoring for the same anatomic volume a challenge, not only for tumors, but also for normal organs-at-risk (OAR). The central hypothesis of this study is that more accurate image registration will lead to improved quantitation of tissue response to RT with 18F-FDG PET/CT. Employing an in-house developed “demons” based deformable image registration algorithm, …

A Smac Mimetic Reduces Tnf Related Apoptosis Inducing Ligand (Trail)-Induced Invasion And Metastasis Of Cholangiocarcinoma Cells., Christian D. Fingas, Boris R.A. Blechacz, Rory L. Smoot, Maria E. Guicciardi, Justin L. Mott, Steve F. Bronk, Nathan W. Werneburg, Alphonse E. Sirica, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

UNLABELLED: Cholangiocarcinoma (CCA) cells paradoxically express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a death ligand that, failing to kill CCA cells, instead promotes their tumorigenicity and especially the metastatic behaviors of cell migration and invasion. Second mitochondria-derived activator of caspase (smac) mimetics are promising cancer therapeutic agents that enhance proapoptotic death receptor signaling by causing cellular degradation of inhibitor of apoptosis (IAP) proteins. Our aim was to examine the in vitro and in vivo effects of the smac mimetic JP1584 in CCA. Despite JP1584-mediated loss of cellular inhibitor of apoptosis-1 (cIAP-1) and cIAP-2, TRAIL failed to induce apoptosis in KMCH-1, …

Transcriptional Suppression Of Mir-29b-1/Mir-29a Promoter By C-Myc, Hedgehog, And Nf-Kappab., Justin L. Mott, Satoshi Kurita, Sophie C. Cazanave, Steven F. Bronk, Nathan W. Werneburg, Martin E. Fernandez-Zapico

Journal Articles: Biochemistry & Molecular Biology

MicroRNAs regulate pathways contributing to oncogenesis, and thus the mechanisms causing dysregulation of microRNA expression in cancer are of significant interest. Mature mir-29b levels are decreased in malignant cells, and this alteration promotes the malignant phenotype, including apoptosis resistance. However, the mechanism responsible for mir-29b suppression is unknown. Here, we examined mir-29 expression from chromosome 7q32 using cholangiocarcinoma cells as a model for mir-29b downregulation. Using 5' rapid amplification of cDNA ends, the transcriptional start site was identified for this microRNA locus. Computational analysis revealed the presence of two putative E-box (Myc-binding) sites, a Gli-binding site, and four NF-kappaB-binding sites …

Immune Recognition Of Self Nucleic Acids Driven By Endogenous Antimicrobial Peptides: Role In Autoimmunity, Dipyaman Ganguly

Dissertations and Theses (Open Access)

Innate immune recognition of extracellular host-derived self-DNA and self-RNA is prevented by endosomal seclusion of the Toll-like receptors (TLRs) in the dendritic cells (DCs). However, in psoriasis plasmacytoid dendritic cells have been found to be able to sense self-DNA molecules in complex with the endogenous cationic antimicrobial peptide LL37, which are internalized into the endosomal compartments and thus can access TLR9. We investigated whether this endogenous peptide can also interact with extracellular self-RNA and lead to DC activation. We found that LL37 binds self-RNA as well as self-DNA going into an electrostatic interaction; forms micro-aggregates of nano-scale particles protected from …