Digital Commons Network^™

Bjc Today

BJC Today

No abstract provided.

Inhibition Of Rev-Erbs Stimulates Microglial Amyloid-Beta Clearance And Reduces Amyloid Plaque Deposition In The 5xfad Mouse Model Of Alzheimer's Disease, Jiyeon Lee, Do Eon Kim, Percy Griffin, Patrick W Sheehan, Dong-Hou Kim, Erik S Musiek, Seung-Yong Yoon

Open Access Publications

A promising new therapeutic target for the treatment of Alzheimer's disease (AD) is the circadian system. Although patients with AD are known to have abnormal circadian rhythms and suffer sleep disturbances, the role of the molecular clock in regulating amyloid-beta (Aβ) pathology is still poorly understood. Here, we explored how the circadian repressors REV-ERBα and β affected Aβ clearance in mouse microglia. We discovered that, at Circadian time 4 (CT4), microglia expressed higher levels of the master clock protein BMAL1 and more rapidly phagocytosed fibrillary Aβ

Hope On The Horizon: Novel Fungal Treatments In Development, Adriana M. Rauseo, Ariella Coler-Reilly, Lindsey Larson, Andrej Spec

Open Access Publications

The treatment of invasive fungal infections remains challenging due to limitations in currently available antifungal therapies including toxicity, interactions, restricted routes of administration, and drug resistance. This review focuses on novel therapies in clinical development, including drugs and a device. These drugs have novel mechanisms of action to overcome resistance, and some offer new formulations providing distinct advantages over current therapies to improve safety profiles and reduce interactions. Among agents that target the cell wall, 2 glucan synthesis inhibitors are discussed (rezafungin and ibrexafungerp), as well as fosmanogepix and nikkomycin Z. Agents that target the cell membrane include 3 fourth-generation …

Hypothalamic Orexin And Mechanistic Target Of Rapamycin Activation Mediate Sleep Dysfunction In A Mouse Model Of Tuberous Sclerosis Complex, Bo Zhang, Dongjun Guo, Lirong Han, Nicholas Rensing, Akiko Satoh, Michael Wong

2020-Current year OA Pubs

Tuberous sclerosis complex (TSC) is a genetic disease related to hyperactivation of the mechanistic target of rapamycin (mTOR) pathway and manifested by neurological symptoms, such as epilepsy and sleep disorders. The pathophysiology of sleep dysfunction is poorly understood and is likely multifactorial, but may involve intrinsic biological regulators in the brain. Here, we characterized a mouse model of sleep disorders in TSC and investigated mechanisms of sleep dysfunction in this conditional knockout model involving inactivation of the Tsc1 gene in neurons and astrocytes (Tsc1

Toward Actionable Practice Parameters For "Dual Diagnosis": Principles Of Assessment And Management For Co-Occurring Psychiatric And Intellectual/Developmental Disability, John N Constantino, Shae Strom, Michael Bunis, Cy Nadler, Teresa Rodgers, Julia Lepage, Connie Cahalan, Amber Stockreef, Lucas Evans, Rachel Jones, Alyssa Wilson

2020-Current year OA Pubs

PURPOSE OF REVIEW: Although treatment algorithms and parameters for best practice are readily available for all major syndromes of psychiatric impairment, the occurrence of psychiatric syndromes in individuals with intellectual and developmental disability (IDD) invokes serious contextual challenges for interpretation of symptoms, diagnosis, and optimization of treatment, both for clinicians and for the service sectors in which care and support of individuals with IDD are delivered. Recognizing that there exist very few definitive resources for best practice under the circumstance of this form of "dual diagnosis," the Missouri Department of Mental Health convened an expert panel to conduct a focused …

Glopid-R Report On Chikungunya, O'Nyong-Nyong And Mayaro Virus, Part 5: Entomological Aspects, L. Pezzi, M. S. Diamond, Et Al.

2020-Current year OA Pubs

The GloPID-R (Global Research Collaboration for Infectious Disease Preparedness) chikungunya (CHIKV), o'nyong-nyong (ONNV) and Mayaro virus (MAYV) Working Group has been established to investigate natural history, epidemiology and clinical aspects of infection by these viruses. Here, we present a report dedicated to entomological aspects of CHIKV, ONNV and MAYV. Recent global expansion of chikungunya virus has been possible because CHIKV established a transmission cycle in urban settings using anthropophilic vectors such as Aedes albopictus and Aedes aegypti. MAYV and ONNV have a more limited geographic distribution, being confined to Africa (ONNV) and central-southern America (MAYV). ONNV is probably maintained through …

Zika Virus Infection In The Developing Mouse Produces Dramatically Different Neuropathology Dependent On Viral Strain, Kevin K. Noguchi, Brant S. Swiney, Sasha L. Williams, Jacob N. Huffman, Katherine Lucas, Sophie H. Wang, Kayla M. Kapral, Amber Li, Krikor T. Dikranian

Open Access Publications

Zika virus (ZIKV) infection during pregnancy has been causally linked to a constellation of neurodevelopmental deformities in the fetus resulting in a disease termed congenital Zika syndrome (CZS). Here we detail how ZIKV infection produces extensive neuropathology in the developing mouse brain and spinal cord of both sexes. Surprisingly, neuropathology differs depending on viral strain with a French Polynesian isolate producing primarily excitotoxicity and a Brazilian isolate being almost exclusively apoptotic but occurring over a prolonged period that is more likely to produce severe hypoplasia. We also show exposure can produce a characteristic pattern of infection that mirrors neuropathology and …

Perfect Timing: Circadian Rhythms, Sleep, And Immunity - An Nih Workshop Summary, Jeffrey A Haspel, Andrew E Gelman, Brian S Kim, Et Al

Open Access Publications

Recent discoveries demonstrate a critical role for circadian rhythms and sleep in immune system homeostasis. Both innate and adaptive immune responses - ranging from leukocyte mobilization, trafficking, and chemotaxis to cytokine release and T cell differentiation -are mediated in a time of day-dependent manner. The National Institutes of Health (NIH) recently sponsored an interdisciplinary workshop, "Sleep Insufficiency, Circadian Misalignment, and the Immune Response," to highlight new research linking sleep and circadian biology to immune function and to identify areas of high translational potential. This Review summarizes topics discussed and highlights immediate opportunities for delineating clinically relevant connections among biological rhythms, …

Lxrs Regulate Features Of Age-Related Macular Degeneration And May Be A Potential Therapeutic Target, Mayur Choudhary, Ebraheim N Ismail, Pei-Li Yao, Faryan Tayyari, Roxana A Radu, Steven Nusinowitz, Michael E Boulton, Rajendra S Apte, Jeffrey W Ruberti, James T Handa, Peter Tontonoz, Goldis Malek

Open Access Publications

Effective treatments and animal models for the most prevalent neurodegenerative form of blindness in elderly people, called age-related macular degeneration (AMD), are lacking. Genome-wide association studies have identified lipid metabolism and inflammation as AMD-associated pathogenic pathways. Given liver X receptors (LXRs), encoded by the nuclear receptor subfamily 1 group H members 2 and 3 (NR1H3 and NR1H2), are master regulators of these pathways, herein we investigated the role of LXR in human and mouse eyes as a function of age and disease and tested the therapeutic potential of targeting LXR. We identified immunopositive LXR fragments in human extracellular early dry …

Mirdb: An Online Database For Prediction Of Functional Microrna Targets, Yuhao Chen, Xiaowei Wang

Open Access Publications

MicroRNAs (miRNAs) are small noncoding RNAs that act as master regulators in many biological processes. miRNAs function mainly by downregulating the expression of their gene targets. Thus, accurate prediction of miRNA targets is critical for characterization of miRNA functions. To this end, we have developed an online database, miRDB, for miRNA target prediction and functional annotations. Recently, we have performed major updates for miRDB. Specifically, by employing an improved algorithm for miRNA target prediction, we now present updated transcriptome-wide target prediction data in miRDB, including 3.5 million predicted targets regulated by 7000 miRNAs in five species. Further, we have implemented …

Diffusion Basis Spectrum Imaging Detects Axonal Loss After Transient Dexamethasone Treatment In Optic Neuritis Mice, Tsen-Hsuan Lin, Jie Zhan, Chunyu Song, Michael Wallendorf, Peng Sun, Xuan Niu, Ruimeng Yang, Anne H Cross, Sheng-Kwei Song

Open Access Publications

Optic neuritis is a frequent first symptom of multiple sclerosis (MS) for which corticosteroids are a widely employed treatment option. The Optic Neuritis Treatment Trial (ONTT) reported that corticosteroid treatment does not improve long-term visual acuity, although the evolution of underlying pathologies is unclear. In this study, we employed non-invasive diffusion basis spectrum imaging (DBSI)-derived fiber volume to quantify 11% axonal loss 2 months after corticosteroid treatment (vs. baseline) in experimental autoimmune encephalomyelitis mouse optic nerves affected by optic neuritis. Longitudinal DBSI was performed at baseline (before immunization), after a 2-week corticosteroid treatment period, and 1 and 2 months after …

The Cartilage Matrisome In Adolescent Idiopathic Scoliosis, Carol A. Wise, Diane Sepich, Aki Ushiki, Anas M. Khanshour, Yared H. Kidane, Nadja Makki, Christina A. Gurnett, Ryan S. Gray, Jonathan J. Rios, Nadav Ahituv, Lila Solnica-Krezel

Open Access Publications

No abstract provided.

Gata2 Regulates Constitutive Pd-L1 And Pd-L2 Expression In Brain Tumors, Yujie Fu, Connor J. Liu, Dale K. Kobayashi, Tanner M. Johanns, Jay A. Bowman-Kirigin, Maximilian O. Schaettler, Diane D. Mao, Diane Bender, Diane G. Kelley, Ravindra Uppaluri, Wenya Linda Bi, Ian F. Dunn, Yu Tao, Jingqin Luo, Albert H. Kim, Gavin P. Dunn

Open Access Publications

No abstract provided.

Feasibility And Safety Of Focused Ultrasound-Enabled Liquid Biopsy In The Brain Of A Porcine Model, Christopher Pham Pacia, Lifei Zhu, Yaoheng Yang, Yimei Yue, Arash Nazeri, H. Michael Gach, Michael R. Talcott, Eric C. Leuthardt, Hong Chen

Open Access Publications

No abstract provided.

Association Of Ptsd Symptom Groups With Functional Impairment And Distress In Trauma-Exposed Disaster Survivors, Carol S North, Erin Van Enkevort, Barry A Hong, Alina M Surís

Open Access Publications

BACKGROUND: In the nearly a quarter of a century since the addition of the clinically significant distress/impairment criterion to the definition of PTSD in DSM-IV, little research has been done to examine the association of this criterion with symptom group criteria and with the numbing subgroup specifically. This study was conducted to examine these relationships in a large database of disaster survivors consistently studied across 12 different incidents of the full range of disaster typology.

METHODS: Analysis was conducted on a merged database representing 1187 trauma-exposed survivors of 12 different disasters studied systematically. DSM-IV-TR criteria for disaster-related PTSD were assessed …

Gene Expression In Meniscal Tears At The Time Of Arthroscopic Partial Meniscectomy Predicts The Progression Of Osteoarthritis Within 6 Years Of Surgery, Joseph D. Lamplot, Muhammad Farooq Rai, William P. Tompkins, Michael V. Friedman, Eric J. Schmidt, Linda J. Sandell, Robert H. Brophy

Open Access Publications

No abstract provided.

Proteomic Resistance Biomarkers For Pi3k Inhibitor In Triple Negative Breast Cancer Patient-Derived Xenograft Models, Zhanfang Guo, Tina Primeau, Jingqin Luo, Cynthia Zhang, Hua Sun, Jeremy Hoog, Feng Gao, Shixia Huang, Dean P Edwards, Sherri R Davies, Rebecca Aft, Li Ding, Matthew J Ellis, Shunqiang Li, Cynthia X Ma

Open Access Publications

PI3K pathway activation is frequently observed in triple negative breast cancer (TNBC). However, single agent PI3K inhibitors have shown limited anti-tumor activity. To investigate biomarkers of response and resistance mechanisms, we tested 17 TNBC patient-derived xenograft (PDX) models representing diverse genomic backgrounds and varying degrees of PI3K pathway signaling activities for their tumor growth response to the pan-PI3K inhibitor, BKM120. Baseline and post-treatment PDX tumors were subjected to reverse phase protein array (RPPA) to identify protein markers associated with tumor growth response. While BKM120 consistently reduced PI3K pathway activity, as demonstrated by reduced levels of phosphorylated AKT, percentage tumor growth …

Simultaneous Immunization With Omp25 And L7/L12 Provides Protection Against Brucellosis In Mice, Sonal Gupta, Surender Mohan, Vikas Kumar Somani, Somya Aggarwal, Rakesh Bhatnagar

Open Access Publications

Currently used

Antiretroviral Therapy Does Not Reduce Tuberculosis Reactivation In A Tuberculosis-Hiv Coinfection Model, Shashank R Ganatra, Shabaana A Khader, Et Al

Open Access Publications

While the advent of combination antiretroviral therapy (ART) has significantly improved survival, tuberculosis (TB) remains the leading cause of death in the HIV-infected population. We used Mycobacterium tuberculosis/simian immunodeficiency virus-coinfected (M. tuberculosis/SIV-coinfected) macaques to model M. tuberculosis/HIV coinfection and study the impact of ART on TB reactivation due to HIV infection. Although ART significantly reduced viral loads and increased CD4+ T cell counts in blood and bronchoalveolar lavage (BAL) samples, it did not reduce the relative risk of SIV-induced TB reactivation in ART-treated macaques in the early phase of treatment. CD4+ T cells were poorly restored specifically in the lung …

A Ventrolateral Medulla-Midline Thalamic Circuit For Hypoglycemic Feeding, B. Sofia Beas, Xinglong Gu, Yan Leng, Omar Koita, Shakira Rodriguez-Gonzalez, Morgan Kindel, Bridget A. Matikainen-Ankney, Rylan S. Larsen, Alexxai V. Kravitz, Mark A. Hoon, Mario A. Penzo

Open Access Publications

No abstract provided.

Washington University Magazine, February 2020

Washington University Magazine

No abstract provided.

Antenatal Corticosteroids In Preterm Small-For-Gestational Age Infants: A Systematic Review And Meta-Analysis, Stephanie A. Blankenship, Kristine E. Brown, Laura E. Simon, Molly J. Stout, Methodius G. Tuuli

Becker Library Publications and Presentations

No abstract provided.

Marrowquant Across Aging And Aplasia: A Digital Pathology Workflow For Quantification Of Bone Marrow Compartments In Histological Sections, Josefine Tratwal, Erica L Scheller, Et Al

Open Access Publications

The bone marrow (BM) exists heterogeneously as hematopoietic/red or adipocytic/yellow marrow depending on skeletal location, age, and physiological condition. Mouse models and patients undergoing radio/chemotherapy or suffering acute BM failure endure rapid adipocytic conversion of the marrow microenvironment, the so-called "red-to-yellow" transition. Following hematopoietic recovery, such as upon BM transplantation, a "yellow-to-red" transition occurs and functional hematopoiesis is restored. Gold Standards to estimate BM cellular composition are pathologists' assessment of hematopoietic cellularity in hematoxylin and eosin (H&E) stained histological sections as well as volumetric measurements of marrow adiposity with contrast-enhanced micro-computerized tomography (CE-μCT) upon osmium-tetroxide lipid staining. Due to user-dependent …

Eflornithine Plus Sulindac For Prevention Of Progression In Familial Adenomatous Polyposis, Carol A. Burke, Paul E. Wise, Et Al

Open Access Publications

No abstract provided.

Differentiating Among Stages Of Cognitive Impairment In Aging: Version 3 Of The Uniform Data Set (Uds) Neuropsychological Test Battery And Moca Index Scores, Hiroko H Dodge, John C Morris, Et Al

Open Access Publications

Introduction: Federally funded Alzheimer's Disease Centers in the United States have been using a standardized neuropsychological test battery as part of the National Alzheimer's Coordinating Center Uniform Data Set (UDS) since 2005. Version 3 (V3) of the UDS replaced the previous version (V2) in 2015. We compared V2 and V3 neuropsychological tests with respect to their ability to distinguish among the Clinical Dementia Rating (CDR) global scores of 0, 0.5, and 1.

Methods: First, we matched participants receiving V2 tests (V2 cohort) and V3 tests (V3 cohort) in their cognitive functions using tests common to both versions. Then, we compared …

Effects Of Cyp46a1 Inhibition On Long-Term-Depression In Hippocampal Slices Ex Vivo And 24s-Hydroxycholesterol Levels In Mice In Vivo, Michael Popiolek, Yukitoshi Izumi, Allen T Hopper, Jing Dai, Silke Miller, Hong-Jin Shu, Charles F Zorumski, Steven Mennerick

Open Access Publications

The manipulation of cholesterol and its metabolites has been hypothesized to be therapeutically beneficial for mood disorders, neurodegenerative disorders, and epilepsies. A major regulator of cholesterol clearance and turnover in the central nervous system is CYP46A1, a brain enriched enzyme responsible for metabolism of cholesterol into 24S-hydroxycholesterol. Inhibition of this enzyme may negatively modulate NMDARs as 24S-hydroxycholesterol was shown to enhance NMDAR function. In addition, alterations of local cholesterol or other changes mediated by CYP46A1 activity could have important influences on central nervous system function. Here we demonstrate that humans and mice display brain region specific and similar CYP46A1 and …

Dendritic And Parallel Processing Of Visual Threats In The Retina Control Defensive Responses, T Kim, N Shen, J-C Hsiang, K P Johnson, D Kerschensteiner

Open Access Publications

Approaching predators cast expanding shadows (i.e., looming) that elicit innate defensive responses in most animals. Where looming is first detected and how critical parameters of predatory approaches are extracted are unclear. In mice, we identify a retinal interneuron (the VG3 amacrine cell) that responds robustly to looming, but not to related forms of motion. Looming-sensitive calcium transients are restricted to a specific layer of the VG3 dendrite arbor, which provides glutamatergic input to two ganglion cells (W3 and OFFα). These projection neurons combine shared excitation with dissimilar inhibition to signal approach onset and speed, respectively. Removal of VG3 amacrine cells …

Antibodies Targeting Epitopes On The Cell-Surface Form Of Ns1 Protect Against Zika Virus Infection During Pregnancy, Alex W. Wessel, Nurgun Kose, Robin G. Bombardi, Vicky Roy, Warangkana Chantima, Juthathip Mongkolsapaya, Melissa A. Edeling, Christopher A. Nelson, Irene Bosch, Galit Alter, Gavin R. Screaton, David H. Fremont, James E. Crowe Jr, Michael S. Diamond

Open Access Publications

No abstract provided.

Chemical Inhibition Of Papd5/7 Rescues Telomerase Function And Hematopoiesis In Dyskeratosis Congenita, Siddharth Shukla, Ho-Chang Jeong, Christopher M. Sturgeon, Roy Parker, Luis Francisco Zirnberger Batista

Open Access Publications

No abstract provided.

Primary Cilia Control Glucose Homeostasis Via Islet Paracrine Interactions, Jing W. Hughes, Jung Hoon Cho, Hannah E. Conway, Michael R. Digruccio, Xue Wen Ng, Henry F. Roseman, Damien Abreu, Fumihiko Urano, David W. Piston

Open Access Publications

No abstract provided.