Digital Commons Network^™

Self-Regulation And Emotional Reactivity In Infants With Prenatal Exposure To Opioids And Alcohol, Kathryn G Beauchamp, Jean Lowe, Ronald M Schrader, Shikhar Shrestha, Crystal Aragón, Natalia Moss, Julia M Stephen, Ludmila N Bakhireva

Pediatrics Research and Scholarship

BACKGROUND: Infants with prenatal substance exposure are at increased risk for developmental problems, with self-regulatory challenges being some of the most pronounced. The current study aimed to investigate the extent to which prenatal substance exposure (alcohol, opioids) impacts infant self-regulation during a relational stressor and the association between self-regulation and infant affect.

METHODS: Participants were 100 mother-child dyads recruited prenatally (Mean = 23.8 gestational weeks) and completed the Still Face Paradigm (SFP) when infants were 5 to 8 months of age (Mean = 6.9 months) as part of an ENRICH prospective birth cohort study. Based on prospective repeated assessment of …

Malignant Cell-Specific Cxcl14 Promotes Tumor Lymphocyte Infiltration In Oral Cavity Squamous Cell Carcinoma, Anuraag Parikh, Juneho Shin, William Faquin, Derrick T Lin, Itay Tirosh, John B Sunwoo, Sidharth V Puram

Open Access Publications

OBJECTIVES: To explore lymphocyte infiltration as a potential mechanism behind CXCL14-mediated tumor growth suppression in oral cavity squamous cell carcinoma (OSCC).

METHODS: We analyzed single cell RNA-sequencing (scRNA-seq) data from OSCC to identify expression changes among malignant cells in lymph nodes (LN) versus primary tumors. CXCL14 expression in murine OSCC cell lines was quantified using qRT-PCR. Short hairpin RNA knockdown of CXCL14 was performed in mouse oral cavity (MOC)1 cells, and CXCL14 overexpression was performed in MOC2 cells. Cells in each condition were injected into C57BL/6 mice with and without T cell depletion, and tumor volume was measured. At 30 …

A Novel Flow Cytometric Assay To Identify Inhibitors Of Rbpj-Dna Interactions, Robert J. Lake, Mark K. Haynes, Kostiantyn Dreval, Rabeya Bilkis, Larry A. Sklar, Hua-Ying Fan

Pathology Research and Scholarship

Notch signaling is often involved in cancer cell initiation and proliferation. Aberrant Notch activation underlies more than 50% of T-cell acute lymphoblastic leukemia (T-ALL); accordingly, chemicals disrupting Notch signaling are of potential to treat Notch-dependent cancer. Here, we developed a flow cytometry-based high-throughput assay to identify compounds that disrupt the interactions of DNA and RBPJ, the major downstream effector of Notch signaling. From 1492 compounds, we identified 18 compounds that disrupt RBPJ-DNA interactions in a dose-dependent manner. Cell-based assays further revealed that auranofin downregulates Notch-dependent transcription and decreases RBPJ-chromatin interactions in cells. Most strikingly, T-ALL cells that depend on Notch …

Cadmium Exposure Activates Akt/Erk Signaling And Pro-Inflammatory Cox-2 Expression In Human Gallbladder Epithelial Cells Via A Ros Dependent Mechanism, Priyanka Sharma, Trevar S. Caldwell, Megan N. Rivera, Rama R. Gullapalli

Pathology Research and Scholarship

Gallbladder cancer (GBC) is the commonest biliary tract cancer with an ill-defined etiology. We examined the role of Cd+2 exposures in a primary human gallbladder (GB) cell line model in this study. Cd+2 exposures induced decreased cell viability, reactive oxygen species (ROS) generation, altered Akt/ERK signaling pathway activation, PGE2 and COX-2 expression in a human primary gallbladder epithelial cell model. Pharmacological inhibitors were used to determine the key drivers of elevated COX-2 expression due to Cd+2 exposure. Our results show Cd+2 causes a dose- dependent reduction in GB cell viability (EC50 value – 18.6 μM). Dose-dependent activation of phospho-Akt and …

Impact Of Annual And Semi-Annual Mass Drug Administration For Lymphatic Filariasis And Onchocerciasis On Hookworm Infection In Côte D'Ivoire, Agodio Loukouri, Aboulaye Méité, Benjamin G. Koudou, Charles W. Goss, Daphne Lew, Gary J. Weil, Eliezer K. N'Goran, Peter U. Fischer

Open Access Publications

Mass Drug Administration (MDA) programs to eliminate Lymphatic Filariasis (LF) in western Africa use the anthelminthics ivermectin plus albendazole. These drugs have the potential to impact also Soil-Transmitted Helminth (STH) infections, since the drugs have a broad range of anthelminthic activity. Integration of preventive chemotherapy efforts for LF, onchocerciasis and STH is recommended by the World Health Organization (WHO) in order to avoid duplication of MDA and to reduce costs. The objective of the current study was to determine whether five semi-annual rounds of community-wide MDA to eliminate LF and onchocerciasis have a greater impact on STH than three annual …

Long Noncoding Rna H19x Is A Key Mediator Of Tgf-Β-Driven Fibrosi, Elena Pachera, Shervin Assassi, Gloria A Salazar, Mara Stellato, Florian Renoux, Adam Wunderlin, Przemyslaw Blyszczuk, Robert Lafyatis, Fina Kurreeman, Jeska De Vries-Bouwstra, Tobias Messemaker, Carol A Feghali-Bostwick, Gerhard Rogler, Wouter T Van Haaften, Gerard Dijkstra, Fiona Oakley, Maurizio Calcagni, Janine Schniering, Britta Maurer, Jörg Hw Distler, Gabriela Kania, Mojca Frank-Bertoncelj, Oliver Distler

Faculty, Staff and Student Publications

TGF-β is a master regulator of fibrosis, driving the differentiation of fibroblasts into apoptosis-resistant myofibroblasts and sustaining the production of extracellular matrix (ECM) components. Here, we identified the nuclear long noncoding RNA (lncRNA) H19X as a master regulator of TGF-β-driven tissue fibrosis. H19X was consistently upregulated in a wide variety of human fibrotic tissues and diseases and was strongly induced by TGF-β, particularly in fibroblasts and fibroblast-related cells. Functional experiments following H19X silencing revealed that H19X was an obligatory factor for TGF-β-induced ECM synthesis as well as differentiation and survival of ECM-producing myofibroblasts. We showed that H19X regulates DDIT4L gene …

The Vaso-Occlusive Pain Crisis In Sickle Cell Disease: Definition, Pathophysiology, And Management., Deepika S. Darbari, Vivien A. Sheehan, Samir K. Ballas

Cardeza Foundation for Hematologic Research

Early diagnosis, treatment, and prevention of a vaso-occlusive crisis (VOC) are critical to the management of patients with sickle cell disease. It is essential to differentiate between VOC-associated pain and chronic pain, hyperalgesia, neuropathy, and neuropathic pain. The pathophysiology of VOCs includes polymerization of abnormal sickle hemoglobin, inflammation, and adhesion. Hydroxyurea, L-glutamine, crizanlizumab, and voxelotor have been approved by the US Food and Drug Administration for reducing the frequency of VOCs; the European Medicines Agency has approved only hydroxyurea. Other novel treatments are in late-stage clinical development in both the United States and the European Union. The development of agents …

The Impact Of Narratives And Active Video Games On Long-Term Moderate-To-Vigorous Physical Activity: A Randomized Controlled Trial Protocol, Dar Alon, Caio Victor Sousa, Tom Baranowski, Tiago V Barreira, Romina Cabrera-Perez, Kelly Chiu, Austin Fernandez, Amy Fleischman, Shirley Huang, Jungyun Hwang, Melanie C Green, I-Min Lee, Kelly Lee, Sarah Lessard, Lynne L Levitsky, Aika Misawa, Farzad Noubary, Ronald Samuels, Kyung Jin Sun, Debbe Thompson, Amy S Lu

Children’s Nutrition Research Center Staff Publications

Background: Although physical activity (PA) has been shown in helping prevent and treat obesity, current PA interventions are still not effective in ameliorating the obesity epidemic. Additional forms of PA need to be investigated to improve PA engagement and outcomes. We hypothesize that pairing a narrative (i.e., story) with an active video game (AVG), a less traditional form of PA, will increase participant engagement in PA. This paper presents the rationale, implementation, and pilot results of a study assessing the effect of narrative's impact on PA and a series of other health outcomes.

Objective: This paper presents the rationale, implementation, …

The Role Of Glia In Protein Aggregation, Qingyun Li, Michael S Haney

2020-Current year OA Pubs

Protein aggregation diseases involve intracellular accumulation or extracellular deposition of certain protein species in neuronal or glial cells, leading to neurodegeneration and shortened lifespan. Prime examples include Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), which are affected by overlapping or specific aggregation-prone proteins. Mounting evidence suggests that dysfunctional glial cells may be major drivers for some diseases, and when they are not causal factors, they could still significantly exacerbate or alleviate disease progression by playing a plethora of detrimental or beneficial roles. Here we review the diverse functions performed by glial cells in …

Immune And Microrna Responses To Infection And Indole-3-Carbinol During Colitis, Rasha Raheem Alkarkoushi, Yvonne Hui, Abbas S. Tavakoli, Udai Singh, Prakash Nagarkatti, Mitzi Nagarkatti, Ioulia Chatzistamou, Marpe Bam, Traci L. Testerman

Faculty Publications

BACKGROUND: Indole-3-carbinol (I3C) and other aryl hydrocarbon receptor agonists are known to modulate the immune system and ameliorate various inflammatory and autoimmune diseases in animal models, including colitis induced by dextran sulfate sodium (DSS). MicroRNAs (miRNAs) are also gaining traction as potential therapeutic agents or diagnostic elements. Enterohepatic (EHH) species are associated with an increased risk of inflammatory bowel disease, but little is known about how these species affect the immune system or response to treatment. AIM: To determine whether infection with an EHH species alters the response to I3C and how the immune and miRNA responses of an EHH …

Structure And Mechanism Of A Unique Diiron Center In Mammalian Stearoyl-Coa Desaturase, Jiemin Shen, Gang Wu, Ah-Lim Tsai, Ming Zhou

Faculty, Staff and Students Publications

Stearoyl-CoA desaturase 1 (SCD1) is a membrane-embedded metalloenzyme that catalyzes formation of a double-bond on a saturated acyl-CoA. SCD1 has a diiron center and its proper function requires an electron transport chain composed of NADH (or NADPH), cytochrome b5 reductase (b5R), and cytochrome b5 (cyt b5). Since SCD1 is a key regulator in fat metabolism and is required for survival of cancer cells, there is intense interest in targeting SCD1 for various metabolic diseases and cancers. Crystal structures of human and mouse SCD1 were reported recently, however, both proteins have two zinc ions instead of two iron ions in the …

Auxora Versus Standard Of Care For The Treatment Of Severe Or Critical Covid-19 Pneumonia: Results From A Randomized Controlled Trial, Joseph B. Miller Md, Charles Bruen, Michael Schnaus, Jeffrey Zhang, Sadia Ali, April Lind, Zachary Stoecker, Kenneth Stauderman, Sudarshan Hebbar

Emergency Medicine Articles

BACKGROUND: Calcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications observed in patients with COVID-19. This study aimed to investigate the safety and efficacy of Auxora, a novel, intravenously administered CRAC channel inhibitor, in adults with severe or critical COVID-19 pneumonia.

METHODS: A randomized, controlled, open-label study of Auxora was conducted in adults with severe or critical COVID-19 pneumonia. Patients were randomized 2:1 to receive three doses of once-daily Auxora versus standard of care (SOC) alone. The primary objective was to assess the safety and tolerability of Auxora. Following FDA …

Comparison Of Repeated Doses Of Ivermectin Versus Ivermectin Plus Albendazole For The Treatment Of Onchocerciasis: A Randomized, Open-Label, Clinical Trial, Linda Batsa Debrah, Kerstin Fischer, Gary Weil, Et Al.

2020-Current year OA Pubs

BACKGROUND: Improved treatment for onchocerciasis is needed to accelerate onchocerciasis elimination in Africa. Aiming to better exploit registered drugs, this study was undertaken to determine whether annual or semiannual treatment with ivermectin (IVM; 200 µg/kg) plus albendazole (ALB; 800 mg single dose) is superior to IVM alone.

METHODS: This trial was performed in Ghana and included 272 participants with microfilariae (MF), who were randomly assigned to 4 treatment arms: (1) IVM annually at 0, 12, and 24 months; (2) IVM semiannually at 0, 6, 12, 18, and 24 months; (3) IVM+ALB annually; or (4) IVM+ALB semiannually. Microfiladermia was determined pretreatment …

Safety, Tolerability, And Immunogenicity Of Plasmodium Falciparum Sporozoite Vaccine Administered By Direct Venous Inoculation To Infants And Young Children: Findings From An Age De-Escalation, Dose-Escalation, Double-Blind, Randomized Controlled Study In Western Kenya, Laura C Steinhardt, Ginnie Abarbanell, Et Al.

2020-Current year OA Pubs

BACKGROUND: The whole Plasmodium falciparum sporozoite (PfSPZ) vaccine is being evaluated for malaria prevention. The vaccine is administered intravenously for maximal efficacy. Direct venous inoculation (DVI) with PfSPZ vaccine has been safe, tolerable, and feasible in adults, but safety data for children and infants are limited.

METHODS: We conducted an age de-escalation, dose-escalation randomized controlled trial in Siaya County, western Kenya. Children and infants (aged 5-9 years, 13-59 months, and 5-12 months) were enrolled into 13 age-dose cohorts of 12 participants and randomized 2:1 to vaccine or normal saline placebo in escalating doses: 1.35 × 105, 2.7 × 105, 4.5 …

Diarrhea As A Potential Cause And Consequence Of Reduced Gut Microbial Diversity Among Undernourished Children In Peru, Saba Rouhani, Nicholas W Griffin, Pablo Peñataro Yori, Jeanette L Gehrig, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H Moulton, Eric R Houpt, Michael J Barratt, Margaret N Kosek, Jeffrey I Gordon

2020-Current year OA Pubs

BACKGROUND: Detrimental effects of diarrhea on child growth and survival are well documented, but details of the underlying mechanisms remain poorly understood. Recent evidence demonstrates that perturbations to normal development of the gut microbiota in early life may contribute to growth faltering and susceptibility to related childhood diseases. We assessed associations between diarrhea, gut microbiota configuration, and childhood growth in the Peruvian Amazon.

METHODS: Growth, diarrhea incidence, illness, pathogen infection, and antibiotic exposure were assessed monthly in a birth cohort of 271 children aged 0-24 months. Gut bacterial diversity and abundances of specific bacterial taxa were quantified by sequencing 16S …

Autophagic Adaptation To Oxidative Stress Alters Peritoneal Residential Macrophage Survival And Ovarian Cancer Metastasis, Houjun Xia, Shasha Li, Xiong Li, Weichao Wang, Yingjie Bian, Shuang Wei, Sara Grove, Weimin Wang, Linda Vatan, J Rebecca Liu, Karen Mclean, Ramandeep Rattan, Adnan R. Munkarah, Jun-Lin Guan, Ilona Kryczek, Weiping Zou

Obstetrics, Gynecology and Women's Health Services Articles

Tumor-associated macrophages (TAMs) affect cancer progression and therapy. Ovarian carcinoma often metastasizes to the peritoneal cavity. Here, we found two peritoneal macrophage subsets in mice bearing ID8 ovarian cancer based on the Tim-4 (T-cell immunoglobulin and mucin domain containing 4) expression. Tim-4+ TAMs were embryonically originated and locally sustained while Tim-4- TAMs were replenished from circulating monocytes. Tim-4+ TAMs, but not Tim-4- TAMs, promoted tumor growth in vivo. Relative to Tim-4- TAMs, Tim-4+ TAMs manifested high oxidative phosphorylation and adapted mitophagy to alleviate oxidative stress. High levels of arginase-1 in Tim-4+ TAMs contributed to potent mitophagy activities via weakened mTORC1 …

Enantiomerically Pure Quinoline-Based Κ-Opioid Receptor Agonists: Chemoenzymatic Synthesis And Pharmacological Evaluation, Benedikt Martin, Dirk Schepmann, Freddy A Bernal, Thomas J Schmidt, Tao Che, Karin Loser, Bernhard Wünsch

2020-Current year OA Pubs

Racemic

Metabolism Of Jq1, An Inhibitor Of Bromodomain And Extra Terminal Bromodomain Proteins, In Human And Mouse Liver Microsomes†, Feng Li, Kevin R Mackenzie, Prashi Jain, Conrad Santini, Damian W Young, Martin M Matzuk

Faculty, Staff and Students Publications

JQ1 is a small-molecule inhibitor of the bromodomain and extra terminal (BET) protein family that potently inhibits the bromodomain testis-specific protein (BRDT), which is essential for spermatogenesis. JQ1 treatment produces a reversible contraceptive effect by targeting the activity of BRDT in mouse male germ cells, validating BRDT as a male contraceptive target. Although JQ1 possesses favourable physical properties, it exhibits a short half-life. Because the details of xenobiotic metabolism play important roles in the optimization of drug candidates and in determining the role of metabolism in drug efficacy, we investigated the metabolism of JQ1 in human and mouse liver microsomes. …

A Global Slc7a7 Knockout Mouse Model Demonstrates Characteristic Phenotypes Of Human Lysinuric Protein Intolerance, Bridget M Stroup, Ronit Marom, Xiaohui Li, Chih-Wei Hsu, Cheng-Yen Chang, Luan D Truong, Brian Dawson, Ingo Grafe, Yuqing Chen, Ming-Ming Jiang, Denise Lanza, Jennie Rose Green, Qin Sun, J P Barrish, Safa Ani, Audrey E Christiansen, John R Seavitt, Mary E Dickinson, Farrah Kheradmand, Jason D Heaney, Brendan Lee, Lindsay C Burrage

Faculty, Staff and Students Publications

Lysinuric protein intolerance (LPI) is an inborn error of cationic amino acid (arginine, lysine, ornithine) transport caused by biallelic pathogenic variants in SLC7A7, which encodes the light subunit of the y+LAT1 transporter. Treatments for the complications of LPI, including growth failure, renal disease, pulmonary alveolar proteinosis, autoimmune disorders and osteoporosis, are limited. Given the early lethality of the only published global Slc7a7 knockout mouse model, a viable animal model to investigate global SLC7A7 deficiency is needed. Hence, we generated two mouse models with global Slc7a7 deficiency (Slc7a7em1Lbu/em1Lbu; Slc7a7Lbu/Lbu and Slc7a7em1(IMPC)Bay/em1(IMPC)Bay; Slc7a7Bay/Bay) using CRISPR/Cas9 technology by introducing a deletion of exons …

Glycan Cross-Feeding Supports Mutualism Between Fusobacterium And The Vaginal Microbiota, Kavita Agarwal, Lloyd S. Robinson, Somya Aggarwal, Lynne R. Foster, Ariel Hernandez-Leyva, Hueylie Lin, Brett A. Tortelli, Valerie P. O'Brien, Liza Miller, Andrew L. Kau, Hilary Reno, Nicole M. Gilbert, Warren G. Lewis, Amanda L. Lewis

Open Access Publications

Women with bacterial vaginosis (BV), an imbalance of the vaginal microbiome, are more likely to be colonized by potential pathogens such as Fusobacterium nucleatum, a bacterium linked with intrauterine infection and preterm birth. However, the conditions and mechanisms supporting pathogen colonization during vaginal dysbiosis remain obscure. We demonstrate that sialidase activity, a diagnostic feature of BV, promoted F. nucleatum foraging and growth on mammalian sialoglycans, a nutrient resource that was otherwise inaccessible because of the lack of endogenous F. nucleatum sialidase. In mice with sialidase-producing vaginal microbiotas, mutant F. nucleatum unable to consume sialic acids was impaired in vaginal colonization. …

Modulation Of Hedgehog Signaling By Kappa Opioids To Attenuate Osteoarthritis, Alexander E Weber, Omid Jalali, Sean Limfat, Ruzanna Shkhyan, Robert Van Der Horst, Siyoung Lee, Yucheng Lin, Liangliang Li, Erik N Mayer, Liming Wang, Nancy Q Liu, Frank A Petrigliano, Jay R Lieberman, Denis Evseenko

Faculty, Staff and Students Publications

OBJECTIVE: Inhibition of hedgehog (HH) signaling prevents cartilage degeneration and promotes repair in animal models of osteoarthritis (OA). This study, undertaken in OA models and in human OA articular cartilage, was designed to explore whether kappa opioid receptor (KOR) modulation via the inhibition of HH signaling may have therapeutic potential for achieving disease-modifying activity in OA.

METHODS: Primary human articular cartilage and synovial tissue samples from patients with knee OA undergoing total joint replacement and from healthy human subjects were obtained from the National Disease Research Interchange. For in vivo animal studies, a partial medial meniscectomy (PMM) model of knee …

Reflections Of The Angiotensin Receptor Blocker Recall By The Fda And Repercussions On Healthcare, Michael Gillette, Addison Taylor, Djenita Butulija, Himabindu Kadiyala, Hani Jneid

Faculty, Staff and Students Publications

PURPOSE: Beginning in July of 2018, the FDA issued a voluntary recall regarding the presence of a contaminant found in the manufacturing of valsartan. What would ensue has become a largely unprecedented sequence of alarming events since the FDA began reporting public recalls, withdrawals and safety alerts on their website in 2016. Since then, the United States has been significantly impacted by drug recalls affecting angiotensin receptor blockers. This report arms clinicians with additional guidance and provides a framework for responding appropriately to future similar incidents and includes an overview of the angiotensin receptor blockers, and their effects and safety …

Tumor Organoids To Study Gastroesophageal Cancer: A Primer, Ramon U Jin, Jason C Mills

2020-Current year OA Pubs

Gastroesophageal cancers are leading causes of cancer death. Our attempts at adopting molecularly based treatment approaches have been slow and ineffective even though we begin to identify specific targetable gene mutations and pathways. It is clear that we should no longer treat all gastroesophageal cancers as a homogeneous disease, which is what we do when we use non-specific chemotherapy. However, we currently cannot monitor successful gene/pathway targeting, nor understand how/when tumors develop resistance, nor predict which patients will derive maximal benefit. To improve outcomes, we must precisely detail the heterogeneity of these tumors to then individualize cancer therapy as well …

Whole Exome Sequencing In Patients With Williams-Beuren Syndrome Followed By Disease Modeling In Mice Points To Four Novel Pathways That May Modify Stenosis Risk, Phoebe C R Parrish, Delong Liu, Russell H Knutsen, Charles J Billington, Robert P Mecham, Yi-Ping Fu, Beth A Kozel

2020-Current year OA Pubs

Supravalvular aortic stenosis (SVAS) is a narrowing of the aorta caused by elastin (ELN) haploinsufficiency. SVAS severity varies among patients with Williams-Beuren syndrome (WBS), a rare disorder that removes one copy of ELN and 25-27 other genes. Twenty percent of children with WBS require one or more invasive and often risky procedures to correct the defect while 30% have no appreciable stenosis, despite sharing the same basic genetic lesion. There is no known medical therapy. Consequently, identifying genes that modify SVAS offers the potential for novel modifier-based therapeutics. To improve statistical power in our rare-disease cohort (N = 104 exomes), …

Transcriptional Profiling Reveals Altered Biological Characteristics Of Chorionic Stem Cells From Women With Gestational Diabetes, Liyun Chen, Chung-Teng Wang, Nicholas R Forsyth, Pensee Wu

Open Access Publications

BACKGROUND: Gestational diabetes (GDM) is a common complication of pregnancy. The impact of pregnancy complications on placental function suggests that extraembryonic stem cells in the placenta may also be affected during pregnancy. Neonatal tissue-derived stem cells, with the advantages of their differentiation capacity and non-invasive isolation processes, have been proposed as a promising therapeutic avenue for GDM management through potential cell therapy approaches. However, the influence of GDM on autologous stem cells remains unclear. Thus, studies that provide comprehensive understanding of stem cells isolated from women with GDM are essential to guide future clinical applications.

METHODS: Human chorionic membrane-derived stem …

Epidemiological Study Of Trichosporon Asahii Infections Over The Past 23 Years, Haitao Li, Meihong Guo, Congmin Wang, Yibo Li, Anne Marie Fernandez, Thomas N Ferraro, Rongya Yang, Yong Chen

College of Science & Mathematics Departmental Research

Trichosporon is a yeast-like basidiomycete, a conditional pathogenic fungus that is rare in the clinic but often causes fatal infections in immunocompromised individuals. Trichosporon asahii is the most common pathogenic fungus in this genus and the occurrence of infections has dramatically increased in recent years. Here, we report a systematic literature review detailing 140 cases of T. asahii infection reported during the past 23 years. Statistical analysis shows that T. asahii infections were most frequently reported within immunodeficient or immunocompromised patients commonly with blood diseases. Antibiotic use, invasive medical equipment and chemotherapy were the leading risk factors for acquiring infection. …

Duodenal Microbiota In Stunted Undernourished Children With Enteropathy, Robert Y Chen, Vanderlene L Kung, Matthew C Hibberd, Janaki Guruge, Blanda Di Luccia, Kazi Ahsan, Elizabeth Kennedy, Jesus Santiago-Borges, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

BACKGROUND: Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health problem. Defining the incidence of this disorder, its pathophysiological features, and its contribution to impaired linear and ponderal growth has been hampered by the difficulty in directly sampling the small intestinal mucosa and microbial community (microbiota).

METHODS: In this study, among 110 young children (mean age, 18 months) with linear growth stunting who were living in an urban slum in Dhaka, Bangladesh, and had not benefited from a nutritional intervention, we performed endoscopy …

Sars-Cov-2 Reverse Genetics Reveals A Variable Infection Gradient In The Respiratory Tract, Yixuan J. Hou, Kenichi Okuda, Caitlin E. Edwards, David R. Martinez, Takanori Asakura, Kenneth H. Dinnon, Takafumi Kato, Rhianna E. Lee, Boyd L. Yount, Teresa M. Mascenik, Gang Chen, Kenneth N. Olivier, Andrew Ghio, Longping V. Tse, Sarah R. Leist, Lisa E. Gralinski, Alexandra Schäfer, Hong Dang, Rodney Gilmore, Satoko Nakano, Ling Sun, M Leslie Fulcher, Alessandra Livraghi-Butrico, Nathan I. Nicely, Mark Cameron, Cheryl Cameron, David J. Kelvin, Aravinda De Silva, David M. Margolis, Alena Markmann, Luther Bartelt, Ross Zumwalt, Fernando J. Martinez, Steven P. Salvatore, Alain Borczuk, Purushothama R. Tata, Vishwaraj Sontake, Adam Kimple, Ilona Jaspers, Wanda K. O'Neal, Scott H. Randell, Richard C. Boucher, Ralph S. Baric

Pathology Research and Scholarship

The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 …

Critical Micrornas And Regulatory Motifs In Cleft Palate Identified By A Conserved Mirna-Tf-Gene Network Approach In Humans And Mice, Aimin Li, Peilin Jia, Saurav Mallik, Rong Fei, Hiroki Yoshioka, Akiko Suzuki, Junichi Iwata, Zhongming Zhao

Faculty, Staff and Student Publications

Cleft palate (CP) is the second most common congenital birth defect. The etiology of CP is complicated, with involvement of various genetic and environmental factors. To investigate the gene regulatory mechanisms, we designed a powerful regulatory analytical approach to identify the conserved regulatory networks in humans and mice, from which we identified critical microRNAs (miRNAs), target genes and regulatory motifs (miRNA-TF-gene) related to CP. Using our manually curated genes and miRNAs with evidence in CP in humans and mice, we constructed miRNA and transcription factor (TF) co-regulation networks for both humans and mice. A consensus regulatory loop (miR17/miR20a-FOXE1-PDGFRA) and eight …

Cross-Serotype Protection Against Group A Streptococcal Infections Induced By Immunization With Spy_2191, Pooja Sanduja, Manish Gupta, Vikas Kumar Somani, Vikas Yadav, Meenakshi Dua, Emanuel Hanski, Abhinay Sharma, Rakesh Bhatnagar, Atul Kumar Johri

Open Access Publications

Group A Streptococcus (GAS) infection causes a range of diseases, but vaccine development is hampered by the high number of serotypes. Here, using reverse vaccinology the authors identify SPy_2191 as a cross-protective vaccine candidate. From 18 initially identified surface proteins, only SPy_2191 is conserved, surface-exposed and inhibits both GAS adhesion and invasion. SPy_2191 immunization in mice generates bactericidal antibodies resulting in opsonophagocytic killing of prevalent and invasive GAS serotypes of different geographical regions, including M1 and M49 (India), M3.1 (Israel), M1 (UK) and M1 (USA). Resident splenocytes show higher interferon-γ and tumor necrosis factor-α secretion upon antigen re-stimulation, suggesting activation …