Digital Commons Network^™

Parasitic Infections Represent A Significant Health Threat Among Recent Immigrants In Chicago, Jesica A. Herrick, Monica Nordstrom, Patrick M. Maloney, Miguel Rodriguez, Kevin Naceanceno, Gloria Gallo, Rojelio Mejia, Ron Hershow

Journal Articles: Epidemiology

Parasitic infections are likely under-recognized among immigrant populations in the USA. We conducted a cross-sectional study to evaluate if such infections have health impacts among recent immigrants in Chicago and to identify predictive factors for parasitic infections. A total of 133 recent immigrants were enrolled, filling out a standardized medical questionnaire and providing blood and stool samples. Appriximately 12% of subjects (15/125) who provided a blood or stool sample for testing were found to have evidence of current or prior infection with a pathogenic parasite, of which Toxocara spp. (8 subjects, 6.4%) and Strongyloides stercoralis (5 subjects, 4%) were most …

Exogenous Flupirtine As Potential Treatment For Cln3 Disease, Katia Maalouf, Joelle Makoukji, Sara Saab, Nadine J. Makhoul, Angelica V. Carmona, Nihar Kinarivala, Noël Ghanem, Paul C. Trippier, Rose-Mary Boustany

Journal Articles: Pharmaceutical Sciences

CLN3 disease is a fatal neurodegenerative disorder affecting children. Hallmarks include brain atrophy, accelerated neuronal apoptosis, and ceramide elevation. Treatment regimens are supportive, highlighting the importance of novel, disease-modifying drugs. Flupirtine and its new allyl carbamate derivative (compound 6) confer neuroprotective effects in CLN3-deficient cells. This study lays the groundwork for investigating beneficial effects in Cln3^Δex7/8 mice. WT/Cln3^Δex7/8 mice received flupirtine/compound 6/vehicle for 14 weeks. Short-term effect of flupirtine or compound 6 was tested using a battery of behavioral testing. For flupirtine, gene expression profiles, astrogliosis, and neuronal cell counts were determined. Flupirtine improved neurobehavioral parameters in …

Single Cell Transcriptomics Implicate Novel Monocyte And T Cell Immune Dysregulation In Sarcoidosis, Lori Garman, Richard C. Pelikan, Astrid Rasmussen, Caleb A. Lareau, Kathryn A. Savoy, Umesh S. Deshmukh, Harini Bagavant, Albert M. Levin, Salim Daouk, Wonder P. Drake, Courtney G. Montgomery

Public Health Sciences Articles

Sarcoidosis is a systemic inflammatory disease characterized by infiltration of immune cells into granulomas. Previous gene expression studies using heterogeneous cell mixtures lack insight into cell-type-specific immune dysregulation. We performed the first single-cell RNA-sequencing study of sarcoidosis in peripheral immune cells in 48 patients and controls. Following unbiased clustering, differentially expressed genes were identified for 18 cell types and bioinformatically assessed for function and pathway enrichment. Our results reveal persistent activation of circulating classical monocytes with subsequent upregulation of trafficking molecules. Specifically, classical monocytes upregulated distinct markers of activation including adhesion molecules, pattern recognition receptors, and chemokine receptors, as well …

Do Cognitive Distortions And Coping Skills Predict Scar Acceptance And Body Esteem In Women With Implantable Cardioverter Defibrillators Or Pacemakers?, Nora Brier

PCOM Psychology Dissertations

The purpose of this study was to examine whether cognitions and coping skills predict scar acceptance and body esteem in women 18 years and older with implantable cardioverter defibrillators (ICDs) or pacemakers. A convenience sample of 272 individuals responded to a Facebook post. The measures were a demographic questionnaire, the Social Problem Solving Inventory-Revised (Short) (SPSI-R:S), the Body Esteem Scale for Adolescents and Adults, the Patient Scar Assessment Questionnaire (PSAQ), the Florida Patient Acceptance Survey, and the Inventory of Cognitive Distortions (ICD). Pearson correlation coefficient results revealed a moderate negative correlation between Negative Problem Orientation (NPO) and Body Esteem (Weight), …

The Relationship Between Chronic Health Conditions And Cognitive Deficits In Children, Adolescents, And Young Adults With Down Syndrome: A Systematic Review, Kellen C Gandy, Heidi A Castillo, Lara Ouellette, Jonathan Castillo, Philip J Lupo, Lisa M Jacola, Karen R Rabin, Kimberly P Raghubar, Maria M Gramatges

Library Staff Publications

BACKGROUND: Individuals with Down syndrome are predisposed to a number of chronic health conditions, but the relationship between these conditions and cognitive ability is not clear. The primary objective of this systematic review is to assess this relationship by evaluating studies that measure cognitive performance in the context of Down syndrome-associated chronic health conditions.

METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Studies included in this review (1) included children, adolescent, and young adult participants with Down syndrome and one or more co-occurring health conditions; (2) were quantitative; …

Systemic Th17 Response In The Presence Of Periodontal Inflammation, Lina J Suárez, Daniel E Vargas, Adriana Rodríguez, Roger M Arce, Nelly S Roa

Faculty, Staff and Student Publications

BACKGROUND: The relationship between periodontitis and the pathogenesis of other inflammatory diseases, such as diabetes, rheumatoid arthritis and obesity has been an important topic of study in recent decades. The Th17 pathway plays a significant role in how local inflammation can influence systemic inflammation in the absence of systemic pathology.

OBJECTIVE: To determine Th17 biased-cells in systemically healthy patients in the presence of generalized chronic periodontitis.

METHODOLOGY: A total of 28 patients were recruited without systemic inflammatory pathology, which was determined by clinical history, the Health Assessment Questionnaire (HAQ) and rheumatoid factor detection. Of these patients, 13 were diagnosed as …

Combined Abdominal Heterotopic Heart And Aorta Transplant Model In Mice, Hao Dun, Li Ye, Yuehui Zhu, Brian W Wong

Open Access Publications

BACKGROUND: Allograft vasculopathy (AV) remains a major obstacle to long-term allograft survival. While the mouse aortic transplantation model has been proven as a useful tool for study of the pathogenesis of AV, simultaneous transplantation of the aorta alongside the transplantation of another organ may reveal more clinically relevant mechanisms that contribute to the pathogenesis of chronic allograft rejection. Therefore, we developed a combined abdominal heart and aorta transplantation model in mice which benefits from reducing animal and drug utilization, while providing an improved model to study the progressive nature of AV.

METHODS: The middle of the infrarenal aorta of the …

Identification And Characterization Of Novel Trpm1 Autoantibodies From Serum Of Patients With Melanoma-Associated Retinopathy, Juliette Varin, Margaret M. Reynolds, Nassima Bouzidi, Sarah Tick, Juliette Wohlschlegel, Ondine Becquart, Christelle Michiels, Olivier Dereure, Robert M. Duvoisin, Catherine W. Morgans, José-Alain Sahel, Quentin Samaran, Bernard Guillot, José S. Pulido, Isabelle Audo, Christina Zeitz

Open Access Publications

Melanoma-associated retinopathy (MAR) is a rare paraneoplastic retinal disorder usually occurring in the context of metastatic melanoma. Patients present with night blindness, photopsias and a constriction of the visual field. MAR is an auto-immune disorder characterized by the production of autoantibodies targeting retinal proteins, especially autoantibodies reacting to the cation channel TRPM1 produced in melanocytes and ON-bipolar cells. TRPM1 has at least three different isoforms which vary in the N-terminal region of the protein. In this study, we report the case of three new MAR patients presenting different anti-TRPM1 autoantibodies reacting to the three isoforms of TRPM1 with variable binding …

Canonical Signaling By Tgf Family Members In Mesenchymal Stromal Cells Is Dispensable For Hematopoietic Niche Maintenance Under Basal And Stress Conditions, Joseph Ryan Krambs, Grazia Abou Ezzi, Juo-Chin Yao, Daniel C. Link

Open Access Publications

Mesenchymal stromal cells are an important component of the bone marrow hematopoietic niche. Prior studies showed that signaling from members of the transforming growth factor (TGF) superfamily in mesenchymal stromal cells is required for normal niche development. Here, we assessed the impact of TGF family signaling on niche maintenance and stress responses by deleting Smad4 in mesenchymal stromal cells at birth, thereby abrogating canonical TGF signaling. No alteration in the number or spatial organization of CXCL12-abundant reticular (CAR) cells, osteoblasts, or adipocytes was observed in Osx-Cre, Smad4fl/fl mice, and expression of key niche factors was normal. Basal hematopoiesis and stress …

Quantitative Definition Of Neurobehavior, Vision, Hearing And Brain Volumes In Macaques Congenitally Exposed To Zika Virus, Michelle R. Koenig, Kevin Noguchi, Et Al.

Open Access Publications

Congenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits. We inoculated five pregnant macaques with ZIKV and mock-inoculated one macaque in the first trimester. Following birth, growth, ocular structure/function, brain structure, hearing, histopathology, and neurobehavior were quantitatively assessed during the first week of life. We identified …

Focused Ultrasound For Safe And Effective Release Of Brain Tumor Biomarkers Into The Peripheral Circulation, Lifei Zhu, Arash Nazeri, Christopher Pham Pacia, Yimei Yue, Hong Chen

Open Access Publications

The development of noninvasive approaches for brain tumor diagnosis and monitoring continues to be a major medical challenge. Although blood-based liquid biopsy has received considerable attention in various cancers, limited progress has been made for brain tumors, at least partly due to the hindrance of tumor biomarker release into the peripheral circulation by the blood-brain barrier. Focused ultrasound (FUS) combined with microbubbles induced BBB disruption has been established as a promising technique for noninvasive and localized brain drug delivery. Building on this established technique, we propose to develop FUS-enabled liquid biopsy technique (FUS-LBx) to enhance the release of brain tumor …

Ige And T Cell Reactivity To A Comprehensive Panel Of Cockroach Allergens In Relation To Disease, Anna Pomés, Véronique Schulten, Jill Glesner, Ricardo Da Silva Antunes, Aaron Sutherland, Leonard B Bacharier, Avraham Beigelman, Paula Busse, April Frazier, Alessandro Sette

Open Access Publications

IgE sensitization to cockroach allergens is associated with development of allergic diseases, such as asthma. To understand the relevance of different cockroach allergens for diagnosis and immunotherapy, a comprehensive analysis of IgE antibody levels and T cell reactivity to an expanded set of cockroach allergens and their relationship to disease was performed in a cohort of USA cockroach sensitized patients. IgE antibody levels to recombinant chitinase and hemocyanin were measured for 23 subjects by custom-made ImmunoCAPs and compared with IgE levels to eight cockroach allergens we previously reported for the same cohort.

Investigating The Effects Of Brainstem Neuronal Adaptation On Cardiovascular Homeostasis., James H Park, Jonathan Gorky, Babatunde Ogunnaike, Rajanikanth Vadigepalli, James S Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Central coordination of cardiovascular function is accomplished, in part, by the baroreceptor reflex, a multi-input multi-output physiological control system that regulates the activity of the parasympathetic and sympathetic nervous systems via interactions among multiple brainstem nuclei. Recent single-cell analyses within the brain revealed that individual neurons within and across brain nuclei exhibit distinct transcriptional states contributing to neuronal function. Such transcriptional heterogeneity complicates the task of understanding how neurons within and across brain nuclei organize and function to process multiple inputs and coordinate cardiovascular functions within the larger context of the baroreceptor reflex. However, prior analysis of brainstem neurons revealed …

Targeting The Tumor Core: Hypoxia-Responsive Nanoparticles For The Delivery Of Chemotherapy To Pancreatic Tumors, Matthew I. Confeld, Babak Mamnoon, Li Feng, Heather Jensen Smith, Priyanka Ray, James Froberg, Jiha Kim, Michael A. Hollingsworth, Mohiuddin Quadir, Yongki Choi, Sanku Mallik

Journal Articles: Eppley Institute

In pancreatic ductal adenocarcinoma (PDAC), early onset of hypoxia triggers remodeling of the extracellular matrix, epithelial-to-mesenchymal transition, increased cell survival, the formation of cancer stem cells, and drug resistance. Hypoxia in PDAC is also associated with the development of collagen-rich, fibrous extracellular stroma (desmoplasia), resulting in severely impaired drug penetration. To overcome these daunting challenges, we created polymer nanoparticles (polymersomes) that target and penetrate pancreatic tumors, reach the hypoxic niches, undergo rapid structural destabilization, and release the encapsulated drugs. In vitro studies indicated a high cellular uptake of the polymersomes and increased cytotoxicity of the drugs under hypoxia compared to …

The Vimentin Rod Domain Blocks P-Selectin-P-Selectin Glycoprotein Ligand 1 Interactions To Attenuate Leukocyte Adhesion To Inflamed Endothelium, Fong Wilson Lam, Cameron August Brown, Christian Valladolid, Dabel Cynthia Emebo, Timothy Gerald Palzkill, Miguel Angel Cruz

Faculty, Staff and Students Publications

Acute inflammation begins with leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) binding to P-selectin on inflamed endothelium and platelets. In pathologic conditions, this process may contribute to secondary organ damage, like sepsis-induced liver injury. Therefore, developing novel therapies to attenuate inflammation may be beneficial. We previously reported that recombinant human vimentin (rhVim) binds P-selectin to block leukocyte adhesion to endothelium and platelets. In this study, we used SPOT-peptide arrays to identify the rod domain as the active region within rhVim that interacts with P-selectin. Indeed, recombinant human rod domain of vimentin (rhRod) binds to P-selectin with high affinity, with in silico modeling …

Single-Nuclei Rna-Seq On Human Retinal Tissue Provides Improved Transcriptome Profiling, Qingnan Liang, Rachayata Dharmat, Leah Owen, Akbar Shakoor, Yumei Li, Sangbae Kim, Albert Vitale, Ivana Kim, Denise Morgan, Shaoheng Liang, Nathaniel Wu, Ken Chen, Margaret M Deangelis, Rui Chen

Faculty, Staff and Students Publications

Single-cell RNA-seq is a powerful tool in decoding the heterogeneity in complex tissues by generating transcriptomic profiles of the individual cell. Here, we report a single-nuclei RNA-seq (snRNA-seq) transcriptomic study on human retinal tissue, which is composed of multiple cell types with distinct functions. Six samples from three healthy donors are profiled and high-quality RNA-seq data is obtained for 5873 single nuclei. All major retinal cell types are observed and marker genes for each cell type are identified. The gene expression of the macular and peripheral retina is compared to each other at cell-type level. Furthermore, our dataset shows an …

Distinct Roles Of Interferon Alpha And Beta In Controlling Chikungunya Virus Replication And Modulating Neutrophil-Mediated Inflammation, Lindsey E Cook, Marissa C Locke, Alissa R Young, Kristen Monte, Matthew L Hedberg, Raeann M Shimak, Kathleen C F Sheehan, Deborah J Veis, Michael S Diamond, Deborah J Lenschow

Open Access Publications

Type I interferons (IFNs) are key mediators of the innate immune response. Although members of this family of cytokines signal through a single shared receptor, biochemical and functional variation exists in response to different IFN subtypes. While previous work has demonstrated that type I IFNs are essential to control infection by chikungunya virus (CHIKV), a globally emerging alphavirus, the contributions of individual IFN subtypes remain undefined. To address this question, we evaluated CHIKV pathogenesis in mice lacking IFN-β (IFN-β knockout [IFN-β-KO] mice or mice treated with an IFN-β-blocking antibody) or IFN-α (IFN regulatory factor 7 knockout [IRF7-KO] mice or mice …

Ultrafast Two-Photon Imaging Of A High-Gain Voltage Indicator In Awake Behaving Mice, Vincent Villette, Mariya Chavarha, Ivan K Dimov, Jonathan Bradley, Lagnajeet Pradhan, Benjamin Mathieu, Stephen W Evans, Simon Chamberland, Dongqing Shi, Renzhi Yang, Benjamin B Kim, Annick Ayon, Abdelali Jalil, François St-Pierre, Mark J Schnitzer, Guoqiang Bi, Katalin Toth, Jun Ding, Stéphane Dieudonné, Michael Z Lin

Faculty, Staff and Students Publications

Optical interrogation of voltage in deep brain locations with cellular resolution would be immensely useful for understanding how neuronal circuits process information. Here, we report ASAP3, a genetically encoded voltage indicator with 51% fluorescence modulation by physiological voltages, submillisecond activation kinetics, and full responsivity under two-photon excitation. We also introduce an ultrafast local volume excitation (ULoVE) method for kilohertz-rate two-photon sampling in vivo with increased stability and sensitivity. Combining a soma-targeted ASAP3 variant and ULoVE, we show single-trial tracking of spikes and subthreshold events for minutes in deep locations, with subcellular resolution and with repeated sampling over days. In the …

Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito

Physiology Faculty Publications

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of …

Immune Globulin Subcutaneous, Human - Klhw 20% For Primary Humoral Immunodeficiency: An Open-Label, Phase Iii Study, John W Sleasman, William R Lumry, Iftikhar Hussain, H James Wedner, James B Harris, Kecia L Courtney, Elsa Mondou, Jiang Lin, Mark R Stein

2010-2019 OA Pubs

No abstract provided.

Dc-Script Deficiency Delays Mouse Mammary Gland Development And Branching Morphogenesis, Chunling Tang, Renske J E Van Den Bijgaart, Maaike W G Looman, Nina Tel-Karthaus, Annemarie M A De Graaf, Susan Gilfillan, Marco Colonna, Marleen Ansems, Gosse J Adema

Open Access Publications

Mammary glands are unique organs in which major adaptive changes occur in morphogenesis and development after birth. Breast cancer is the most common cancer and a major cause of mortality in females worldwide. We have previously identified the loss of expression of the transcription regulator DC-SCRIPT (Zfp366) as a prominent prognostic event in estrogen receptor positive breast cancer patients. DC-SCRIPT affects multiple transcriptional events in breast cancer cells, including estrogen and progesterone receptor-mediated transcription, and promotes CDKN2B-related cell cycle arrest. As loss of DC-SCRIPT expression appears an early event in breast cancer development, we here investigated the role of DC-SCRIPT …

Irak4 Mediates Colitis-Induced Tumorigenesis And Chemoresistance In Colorectal Cancer, Qiong Li, Yali Chen, Daoxiang Zhang, Julie Grossman, Lin Li, Namrata Khurana, Hongmei Jiang, Patrick M Grierson, John Herndon, David G Denardo, Grant A Challen, Jingxia Liu, Marianna B Ruzinova, Ryan C Fields, Kian-Huat Lim

Open Access Publications

Aberrant activation of the NF-κB transcription factors underlies chemoresistance in various cancer types, including colorectal cancer (CRC). Targeting the activating mechanisms, particularly with inhibitors to the upstream IκB kinase (IKK) complex, is a promising strategy to augment the effect of chemotherapy. However, clinical success has been limited, largely because of low specificity and toxicities of tested compounds. In solid cancers, the IKKs are driven predominantly by the Toll-like receptor (TLR)/IL-1 receptor family members, which signal through the IL-1 receptor-associated kinases (IRAKs), with isoform 4 (IRAK4) being the most critical. The pathogenic role and therapeutic value of IRAK4 in CRC have …

Multiple Sclerosis Outcomes After Cancer Immunotherapy, Catherine R. Garcia, Rani Jayswal, Val R. Adams, Lowell B. Anthony, John L. Villano

Markey Cancer Center Faculty Publications

INTRODUCTION: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes.

METHODS: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution.

RESULTS: We identified 14 cases of MS …

Stub1 Suppresseses Tumorigenesis And Chemoresistance Through Antagonizing Yap1 Signaling, Dong-E Tang, Yong Dai, Lie-Wen Lin, Yong Xu, Dong-Zhou Liu, Xiao-Ping Hong, Hao-Wu Jiang, Song-Hui Xu

Open Access Publications

Yes-associated protein (YAP) is a component of the canonical Hippo signaling pathway that is known to play essential roles in modulating organ size, development, and tumorigenesis. Activation or upregulation of YAP1, which contributes to cancer cell survival and chemoresistance, has been verified in different types of human cancers. However, the molecular mechanism of YAP1 upregulation in cancer is still unclear. Here we report that the E3 ubiquitin ligase STUB1 ubiquitinates and destabilizes YAP1, thereby inhibiting cancer cell survival. Low levels of STUB1 expression were correlated with increased protein levels of YAP1 in human gastric cancer cell lines and patient samples. …

Imatinib Mesylate Effects On Zebrafish Reproductive Success: Gonadal Development, Gamete Quality, Fertility, Embryo-Larvae Viability And Development, And Related Genes, Nader Ahmadi, Seyed-Mohammadreza Samaee, Robert A. Yokel, Aliasghar Tehrani

Pharmaceutical Sciences Faculty Publications

Imatinib (IM) is a tyrosine kinase (TK) inhibitor (TKI) used to treat chronic myeloid leukemia. Clinical case reports and a few laboratory mammal studies provide inconclusive evidence about its deleterious effects on reproduction. The aim of the current study was to evaluate the potential of zebrafish to characterize IM-induced effects on reproduction and clarify IM effects on reproductive success. To this end, we exposed adult zebrafish to four concentrations of IM for 30 days followed by a 30-day depuration period. IM exposure caused a concentration-dependent, irreversible, suppression of folliculogenesis, reversible decrease in sperm density and motility, decreased fecundity and fertility, …

Becoming As Suffering: A Genealogy Of Female Suffering In Chinese Myth And Literature, Peina Zhuang, Jiazhao Lin

CLCWeb: Comparative Literature and Culture

In their article “Suffering as Becoming: A Genealogy of Female Suffering in Chinese Myth and Literature,” Peina Zhuang and Jiazhao Lin undertake a comparative study of three Chinese mythical and literary novels: the Chinese myths of Chang’eh, Ding Ling’s Miss Sophie’s (1928), and Bi Feiyu’s novel The Moon Opera (1999). They focus on the point that the characterization of all three women (or female personae) is centered on their common act of taking some sort of medicine. However, they also historicize and politicize these three texts, setting them respectively in the contexts of the establishment of patriarchy in the Han …

Virus-Induced Cochlear Inflammation In Newborn Mice Alters Auditory Function, Cathy Yea Won Sung, Maria C. Seleme, Shelby Payne, Stipan Jonjic, Keiko Hirose, William Britt

Open Access Publications

Although human cytomegalovirus (HCMV) is a known cause of sensorineural hearing loss in infants with congenital HCMV (cCMV) infections, mechanisms that contribute to sensorineural hearing loss (SNHL) in infants with cCMV infection are not well defined. Using a murine model of CMV infection during auditory development, we have shown that peripheral infection of newborn mice with murine CMV (MCMV) results in focal infection of the cochlea and virus-induced cochlear inflammation. Approximately 50%-60% of infected mice exhibited increased auditory brainstem response (ABR) thresholds across a range of sound frequencies. Histological analyses of the cochlea in MCMV-infected mice with elevated ABR thresholds …

Vincristine And Bortezomib Use Distinct Upstream Mechanisms To Activate A Common Sarm1-Dependent Axon Degeneration Program, Stefanie Geisler, Ryan A Doan, Galen C Cheng, Aysel Cetinkaya-Fisgin, Shay X Huang, Ahmet Höke, Jeffrey Milbrandt, Aaron Diantonio

Open Access Publications

Chemotherapy-induced peripheral neuropathy is one of the most prevalent dose-limiting toxicities of anticancer therapy. Development of effective therapies to prevent chemotherapy-induced neuropathies could be enabled by a mechanistic understanding of axonal breakdown following exposure to neuropathy-causing agents. Here, we reveal the molecular mechanisms underlying axon degeneration induced by 2 widely used chemotherapeutic agents with distinct mechanisms of action: vincristine and bortezomib. We showed previously that genetic deletion of SARM1 blocks vincristine-induced neuropathy and demonstrate here that it also prevents axon destruction following administration of bortezomib in vitro and in vivo. Using cultured neurons, we found that vincristine and bortezomib converge …

Dhx33 Interacts With Ap-2Β To Regulate Bcl-2 Gene Expression And Promote Cancer Cell Survival, Jiuling Wang, Weimin Feng, Zhen Yuan, Jason D. Weber, Yandong Zhang

Open Access Publications

The RNA helicase DHX33 has been found to be overexpressed in human cancers, where it promotes cancer development. Previous reports have shown that DHX33 deficiency caused cancer cell apoptosis, but the underlying mechanism remains unknown. In this study, we discovered that DHX33 regulates Bcl-2 family protein expression. In multiple human cancer cell lines, DHX33 was found to stimulate the transcription of

Vitamin D Status And Risk Of Incident Tuberculosis Disease: A Nested Case-Control Study, Systematic Review, And Individual-Participant Data Meta-Analysis, Omowunmi Aibana, Chuan-Chin Huang, Said Aboud, Alberto Arnedo-Pena, Mercedes C Becerra, Juan Bautista Bellido-Blasco, Ramesh Bhosale, Roger Calderon, Silvia Chiang, Carmen Contreras, Ganmaa Davaasambuu, Wafaie W Fawzi, Molly F Franke, Jerome T Galea, Daniel Garcia-Ferrer, Maria Gil-Fortuño, Barbará Gomila-Sard, Amita Gupta, Nikhil Gupte, Rabia Hussain, Jesus Iborra-Millet, Najeeha T Iqbal, Jose Vicente Juan-Cerdán, Aarti Kinikar, Leonid Lecca, Vidya Mave, Noemi Meseguer-Ferrer, Grace Montepiedra, Ferdinand M Mugusi, Olumuyiwa A Owolabi, Julie Parsonnet, Freddy Roach-Poblete, Maria Angeles Romeu-García, Stephen A Spector, Christopher R Sudfeld, Mark W Tenforde, Toyin O Togun, Rosa Yataco, Zibiao Zhang, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.

METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. …