Medicine and Health Sciences Commons^™

Effects Of The Gut Microbiota On Placental Angiogenesis And Intrauterine Growth In Gnotobiotic Mice, Reyan Coskun, Zenan L Chang, Athziri Marcial Rodríguez, Haoxin Liu, Jiye Cheng, Yael Alippe, Michael S Diamond, Jeffrey I Gordon

2020-Current year OA Pubs

Environmental causes of intrauterine growth restriction (IUGR) remain poorly characterized. Here, we compare germ-free (GF) and conventionally raised (CONV-R) mice to assess the effects of the gut microbiota on placental/fetal development at embryonic day (E)11.5 (end of placentation) and E17.5 (near term). Pregnancy- and microbiota-associated changes in gene expression occur along the gut, including those related to angiogenesis, while bacterial composition and fermentation activity remain stable. Placental weights at E11.5 and fetal weights at E17.5 are significantly reduced in GF animals. Compared to CONV-R dams, the GF maternal decidua exhibits similar vascular histomorphometric features at E11.5 and E17.5, and numbers …

Let's Doff: A Gown Conservation Strategy For Multidrug-Resistant Organism Colonization During The Covid-19 Pandemic And Beyond, Kelsey L Rowe, Josephine Fox, Carole Leone, Lydia J Grimes, Kenneth Whalen, David K Warren, Jonas Marschall

2020-Current year OA Pubs

A COVID-19 pandemic gown conservation strategy for methicillin-resistant

The Biophysical Basis For Karyopherin-Dependent Ebola Virus Vp24 Nuclear Transport, Junjie Zhao, Bojie Zhang, Olivia Vogel, Benjamin W Walker, Leonard W Ma, Nicole D Wagner, Christopher F Basler, Daisy W Leung, Michael L Gross, Gaya K Amarasinghe

2020-Current year OA Pubs

Nucleocytoplasmic trafficking is a highly regulated process that allows the cell to control the partitioning of proteins and nucleic acids between the cytosolic and nuclear compartments. The Ebola virus minor matrix protein VP24 (eVP24) hijacks this process by binding to a region on the NPI-1 subfamily of karyopherin alpha (KPNA) nuclear importers. This region overlaps with the activated transcription factor STAT1 binding site on KPNAs, preventing STAT1 nuclear localization and activation of antiviral gene transcription. However, the molecular interactions of eVP24-KPNA5 binding that lead to the nuclear localization of eVP24 remain poorly characterized. Here, we show that trafficking of eVP24 …

Artificial Intelligence-Assisted Compressed Sensing Cine Enhances The Workflow Of Cardiac Magnetic Resonance In Challenging Patients, Huaijun Wang, Anne Schmieder, Mary Watkins, Pengjun Wang, Joshua Mitchell, S Zyad Qamer, Gregory Lanza

2020-Current year OA Pubs

BACKGROUND: A key cardiac magnetic resonance (CMR) challenge is breath-holding duration, difficult for cardiac patients.

AIM: To evaluate whether artificial intelligence-assisted compressed sensing CINE (AI-CS-CINE) reduces image acquisition time of CMR compared to conventional CINE (C-CINE).

METHODS: Cardio-oncology patients (

RESULTS: In 89 participants (58.5 ± 16.8 years, 42 males, 47 females), total AI-CS-CINE acquisition and reconstruction time (37 seconds) was 84% faster than C-CINE (238 seconds). C-CINE required repeats in 23% (20/89) of cases (approximately 8 minutes lost), while AI-CS-CINE only needed one repeat (1%; 2 seconds lost). AI-CS-CINE had slightly lower contrast but preserved structural clarity. Bland-Altman plots …

Pilot Study Of [11c]Hy-2-15: A Mixed Alpha-Synuclein And Tau Pet Radiotracer, Chia-Ju Hsieh, Dinahlee Saturnino Guarino, Anthony J Young, Andrew D Siderowf, Ilya Nasrallah, Alexander Schmitz, Carol Garcia, Ho Young Kim, Erin K Schubert, Hsiaoju Lee, Joel S Perlmutter, Robert H Mach

2020-Current year OA Pubs

A novel brain positron emission tomography (PET) radioligand, [

Replication Of Sensor-Based Categorization Of Upper-Limb Performance In Daily Life In People Post Stroke And Generalizability To Other Populations, Chelsea E Macpherson, Marghuretta D Bland, Christine Gordon, Allison E Miller, Caitlin Newman, Carey L Holleran, Christopher J Dy, Lindsay Peterson, Keith R Lohse, Catherine E Lang

2020-Current year OA Pubs

BACKGROUND: Wearable movement sensors can measure upper limb (UL) activity, but single variables may not capture the full picture. This study aimed to replicate prior work identifying five multivariate categories of UL activity performance in people with stroke and controls and expand those findings to other UL conditions.

METHODS: Demographic, self-report, and wearable sensor-based UL activity performance variables were collected from 324 participants (stroke

RESULTS: Two PCs explained 70-90% variance: PC1 (overall UL activity performance) and PC2 (preferred-limb use). A five-variable, five-cluster model was optimal across samples. In comparison to clusters, two PCs and individual accelerometry variables showed higher convergent …

U-Rich Elements Drive Pervasive Cryptic Splicing In 3' Utr Massively Parallel Reporter Assays, Khoa Dao, Courtney F Jungers, Sergej Djuranovic, Anthony M Mustoe

2020-Current year OA Pubs

Untranslated RNA sequences play essential roles in orchestrating gene expression. However, the sequence codes and mechanisms underpinning post-transcriptional regulation remain incompletely understood. Here, we revisit the finding from a prior massively parallel reporter assay (MPRA) that AU-rich elements in 3' untranslated regions (3' UTRs) can drive upregulation or downregulation of mRNA expression depending on 3' UTR context. We unexpectedly discover that this variable regulation arises from widespread cryptic splicing, predominately from an unannotated splice donor in the coding sequence of GFP to diverse acceptor sites in reporter 3' UTRs. Splicing is activated by U-rich sequences, which function as potent position-dependent …

Sepsis Restructures The Mitochondrial Calcium Uniporter Complex In The Lymphoid Tissues Of Mice And Humans, Xianghong Zhang, Jianguo Lin, Baobo Zou, Jack R Killinger, Andrew C Sayce, Thiagarajan Meyyappan, Zeyu Xiong, Melanie J Scott, Janet S Lee, Matthew R Rosengart

2020-Current year OA Pubs

Survivors of sepsis suffer from an elevated risk of premature death that is not explained by a higher burden of chronic diseases prior to the infection. Nearly 1 out of 4 survivors have persistent elevations of inflammation biomarkers, such as interleukin (IL) 6. These observations suggest that sepsis imparts durable changes to organismal biology. Eukaryotic life depends upon ATP and calcium (Ca

Macrophage-T Cell Interactions Promote Slamf1 Expression For Enhanced Tb Defense, G V R Krishna Prasad, Steven J Grigsby, Gideon A Erkenswick, Cynthia Portal-Celhay, Ekansh Mittal, Guozhe Yang, Samuel M Fallon, Fengyixin Chen, Thais Klevorn, Neharika Jain, Yuanyuan Li, Makedonka Mitreva, Amanda J Martinot, Joel D Ernst, Jennifer A Philips

2020-Current year OA Pubs

CD4+ T cells are crucial for protective immunity to intracellular pathogens. In addition to secreting cytokines, CD4+ T cells promote control of Mycobacterium tuberculosis infection through cognate interactions with macrophages, but the mechanism has been unclear. Here, we show that SLAMF1/CD150 is highly and uniquely induced in macrophages by antigen-specific interactions with CD4+ T cells. In macrophages, SLAMF1 enhances the generation of reactive oxygen species and restricts Mtb replication. Mtb-infection of mice promotes SLAMF1 expression specifically on infected macrophages, not uninfected bystanders. SLAMF1 expression depends on adaptive immunity and also autophagy. Moreover, Slamf1

Gene Therapy Ameliorates Neuromuscular Pathology In Cln3 Disease, Ewa A Ziółkowska, Albina Jablonka-Shariff, Letitia L Williams, Matthew J Jansen, Sophie H Wang, Elizabeth M Eultgen, Matthew D Wood, Daniel A Hunter, Jaiprakash Sharma, Marco Sardiello, Robyn Reese, Alan Pestronk, Mark S Sands, Alison K Snyder-Warwick, Jonathan D Cooper

2020-Current year OA Pubs

CLN3 disease is a neuronopathic lysosomal storage disorder that severely impacts the central nervous system (CNS) while also inducing notable peripheral neuromuscular symptoms. Although considerable attention has been directed towards the neurodegenerative consequences within the CNS, the involvement of peripheral tissues, including skeletal muscles and their innervation, has been largely neglected. We hypothesized that, CLN3 deficiency could directly influence peripheral nerves and investigated the neuromuscular system in Cln3

Belumosudil Reduces Oral Chronic Graft-Versus-Host Disease Tissue Inflammation And Fibrosis: A Rockstar Companion Study, Rubina Sharma, Iskra Pusic, Et Al.

2020-Current year OA Pubs

Belumosudil (KD025), an oral, selective, Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2) inhibitor, is approved for third-line treatment of chronic graft-versus-host disease (cGVHD). Previous studies demonstrated that ROCK2 inhibition reduces blood interleukin-17 (IL-17) activity and promotes regulatory T-cell (Treg cell) recovery. However, these studies did not evaluate immune responses within cGVHD-affected tissues. This study assessed tissue-level immune dynamics in 20 patients with oral cGVHD from the phase 2 ROCKstar trial, before and after 6 months of belumosudil treatment, focusing on key effector sites (oral mucosa [OM], minor salivary glands [MSGs], and skin) and the peripheral blood. After belumosudil treatment, reduction in …

The Moderating And Mediating Role Of Resilience In The Relationship Between Adverse Childhood Experiences And Depression, Ptsd, And Suicidality In Kenyan Youth, Victoria Mutiso, David Ndetei, Eric Jeremiah, Pascalyne Nyamai, Samuel Walusaka, Veronica Onyango, Christine Musyimi, Kamaldeep Bhui, Daniel Mamah

2020-Current year OA Pubs

Adverse childhood experiences (ACEs) are widely associated with mental health disorders, such as depression, post-traumatic stress disorder (PTSD), and suicidality. Resilience plays a role in mediation and moderation of these associations, yet there is limited data from Kenya on this. This cross-sectional study examined the role of resilience in the relationship between ACEs and mental health outcomes among 1,972 participants aged 14-25 years in the Nairobi Metropolitan area. Participants completed the Trauma and Distress Scale (ACEs), Patient Health Questionnaire-9 (depression), Columbia-Suicide Severity Rating Scale (suicidality), Harvard Trauma Questionnaire (PTSD), and Adult Resilience Measure-Revised (resilience). Analyses of moderation and mediation using …

Unlocking Efficiency In Real-World Collaborative Studies: A Multi-Site International Study With One-Shot Lossless Glmm Algorithm, Jiayi Tong, Chongliang Luo, Et Al.

2020-Current year OA Pubs

The widespread adoption of real-world data has given rise to numerous healthcare-distributed research networks, but multi-site analyses still face administrative burdens and data privacy challenges. In response, we developed a Collaborative One-shot Lossless Algorithm for Generalized Linear Mixed Models (COLA-GLMM), the first-ever algorithm that achieves both lossless and one-shot properties. COLA-GLMM ensures accuracy against the gold standard of pooled data while requiring only summary statistics and completes within a single communication round, eliminating the usual back-and-forth overhead. We further introduced an enhanced version that employs homomorphic encryption to reduce the risks of summary statistics misuse at the coordinating center. The …

Autoregulation Of Rpl7b By Inhibition Of A Structural Splicing Enhancer, David Granas, Ishan Gammadde Hewa, Michael A White, Gary D Stormo

2020-Current year OA Pubs

Yeast ribosomal protein gene RPL7B is autoregulated by inhibition of splicing. The first intron has a "zipper stem" that brings the 5' splice site near the branch point (BP) and serves as an enhancer of splicing that is required for efficient splicing because the intron has a nonconsensus BP sequence of UGCUAAC. The intron also contains an alternative, and mutually exclusive, structure that is conserved across many yeast species. That conserved structure is a binding site for the Rpl7 protein so that when the protein is in excess over what is required for ribosomes, the protein binds to the conserved …

Chondrocyte-Specific Knockout Of Piezo1 And Piezo2 Protects Against Post-Traumatic Osteoarthritis Structural Damage And Pain In Mice, Erica V Ely, Kristin L Lenz, Sophie G Paradi, Seth Ack, Abraham Behrmann, Sarah Dunivan, Lauryn Braxton, Wolfgang Liedtke, Yong Chen, Kelsey H Collins, Farshid Guilak

2020-Current year OA Pubs

BACKGROUND: Osteoarthritis (OA) is a debilitating joint disease characterized by cartilage degeneration, synovial inflammation, and bone remodeling, with limited therapeutic options targeting the underlying pathophysiology. Mechanosensitive ion channels Piezo1 and Piezo2 play crucial roles in chondrocyte responses to mechanical stress, mediating mechanotransduction pathways that influence chondrocyte survival, matrix production, and inflammatory signaling, but their distinct contributions to OA pathogenesis remain unclear.

METHODS: Using inducible, chondrocyte-specific Aggrecan-Cre (Acan) mice, we investigated Piezo1, Piezo2, and combined Piezo1/2 conditional knockouts (cKOs) using the destabilization of the medial meniscus (DMM) model of post-traumatic OA in male and female mice. Pain and behavioral assessments were …

Discovery Of N-(6-Methoxypyridin-3-Yl)Quinoline-2-Amine Derivatives For Imaging Aggregated Α-Synuclein In Parkinson's Disease With Positron Emission Tomography, Haiyang Zhao, Tianyu Huang, Dhruva D Dhavale, Jennifer Y O'Shea, Jiwei Gu, Xuyi Yue, Ying-Hwey Nai, Hao Jiang, Paul T Kotzbauer, Joel S Perlmutter, Zhude Tu, Et Al.

2020-Current year OA Pubs

The fibrillary aggregation of α-synuclein is a hallmark of Parkinson's disease (PD) and a potential target for diagnostics and therapeutics. Although substantial effort has been devoted to the development of positron emission tomography (PET) probes for detecting α-synuclein aggregates, no clinically suitable tracer has been reported. The design and synthesis of 43 new

Cdc1s Promote Atherosclerosis Via Local Immunity And Are Targetable For Therapy, Miguel Galán, Suin Jo, Tian-Tian Liu, Kenneth M. Murphy, Et Al.

2020-Current year OA Pubs

BACKGROUND: Atherosclerosis is characterized by immune cell accumulation in the arterial wall and adaptive CD4

METHODS: We tested atherosclerosis in

RESULTS: Expansion of DCs in

CONCLUSIONS: Using state-of-the-art strategies, our results establish that cDC1s have a proatherogenic role in atherosclerosis by boosting CD4

Brain Functional Connectivity Correlates Of Autism Diagnosis And Familial Liability In 24-Month-Olds, John R Pruett Jr, Alexandre A Todorov, Muhamed Talovic, Tomoyuki Nishino, Steven E Petersen, Savannah Davis, Lyn Stahl, Kelly N Botteron, Natasha Marrus, Robert C Mckinstry, William D Shannon, Abraham Z Snyder, Et Al.

2020-Current year OA Pubs

BACKGROUND: fcMRI correlates of autism spectrum disorder (ASD) diagnosis and familial liability were studied in 24-month-olds at high (older affected sibling) and low familial likelihood for ASD.

METHODS: fcMRI comparisons of high-familial-likelihood (HL) ASD-positive (HLP, N = 23) and ASD-negative (HLN, N = 91), and low-likelihood ASD-negative (LLN, N = 27) 24-month-olds from the Infant Brain Imaging Study (IBIS) Network were conducted, employing object oriented data analysis (OODA), support vector machine (SVM) classification, and network-level fcMRI enrichment analyses.

RESULTS: OODA (alpha = 0.0167, 3 comparisons) revealed differences in HLP and LLN fcMRI matrices (p = 0.012), but none for HLP …

Cryo-Em Structures Of A Pentameric Ligand-Gated Ion Channel In Liposomes, Vikram Dalal, Brandon K Tan, Hanrui Xu, Wayland W L Cheng

2020-Current year OA Pubs

Detergents and lipid nanodiscs affect the cryo-EM structures of pentameric ligand-gated ion channels (pLGICs) including ELIC. To determine the structure of a pLGIC in a membrane environment that supports ion channel function, we performed single particle cryo-EM of ELIC in liposomes. ELIC activation and desensitization were confirmed in liposomes with a stopped-flow thallium flux assay. Using WT ELIC and a non-desensitizing mutant (ELIC5), we captured resting, activated, and desensitized structures at high resolution. In the desensitized structure, the ion conduction pore has a constriction at the 9' leucine of the pore-lining M2 helix, indicating that 9' is the desensitization gate …

V2b Neurons Act Via Multiple Targets To Produce In Phase Inhibition During Locomotion, Mohini Sengupta, Alaina Bertram, Shuyu Iris Zhu, Geoffrey J Goodhill, Martha W Bagnall

2020-Current year OA Pubs

Spinal interneurons shape motor neuron activity. Gata3

Identification Of Functional Non-Coding Variants Associated With Orofacial Cleft, Priyanka Kumari, Ryan Z Friedman, Michael A White, Barak A Cohen, Et Al.

2020-Current year OA Pubs

Oral facial cleft (OFC) comprises cleft lip with or without cleft palate (CL/P) or cleft palate only. Genome wide association studies (GWAS) of isolated OFC have identified common single nucleotide polymorphisms (SNPs) in many genomic loci where the presumed effector gene (for example, IRF6 in the 1q32 locus) is expressed in embryonic oral epithelium. To identify candidates for functional SNPs at eight such loci we conduct a massively parallel reporter assay in a fetal oral epithelial cell line, revealing SNPs with allele-specific effects on enhancer activity. We filter these SNPs against chromatin-mark evidence of enhancers and test a subset in …

Targeting Triple-Negative Breast Cancer With Momordicine-I For Therapeutic Gain In Preclinical Models, Kousik Kesh, Ellen T Tran, Ruchi A Patel, Cynthia X Ma, Ratna B Ray

2020-Current year OA Pubs

No abstract provided.

Integrated Genomic Analysis Of Nf1-Associated Peripheral Nerve Sheath Tumors: An Updated Biorepository Dataset, Jineta Banerjee, Yang Lyu, Kuangying Yang, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

Neurofibromatosis type 1 (NF1) is an inherited neurocutaneous condition that predisposes to the development of peripheral nerve sheath tumors (PNST) including cutaneous neurofibromas (CNF), plexiform neurofibromas (PNF), atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP), and malignant peripheral nerve sheath tumors (MPNST). The Johns Hopkins NF1 biospecimen repository promotes the successful advancement of therapeutic developments for NF1-associated PNST through acquisition and genomic analysis of human tumor specimens. RNA sequencing (RNAseq) and whole exome sequencing (WES) data were generated from 73 and 114 primary human tumor samples, respectively. These pre-processed data, standardized for immediate computational analysis, are accessible through the NF …

Heart Failure With Reduced Ejection Fraction Polypill Implementation Strategy In Sri Lanka: Design And Protocol Of A Pilot Type I Hybrid Randomised Clinical Trial, Anubha Agarwal, Mansi Agarwal, Charles W. Goss, Adam Hively, Mark D. Huffman, Et Al.

2020-Current year OA Pubs

No abstract provided.

Ablation Of The Evolutionarily Acquired Functions Of The Atp1b4 Gene Increases Metabolic Capacity And Reduces Obesity, Nikolai N Modyanov, Lucia Russo, Sumona Ghosh Lester, Tamara R Castañeda, Himangi G Marathe, Larisa V Fedorova, Raymond E Bourey, Sonia M Najjar, Ivana L De La Serna

2020-Current year OA Pubs

In placental mammals, the co-option of vertebrate orthologous

Comparative Analysis Of Hiv Data Completeness In Haiti's Isanté Plus Electronic Medical Record System Across Children, Adolescents And Adults: A Cross-Sectional Evaluation Of 2016-2022 Data, Beryne Odeny, Jean Guy Honoré, Jean Gabriel Balan, James P Hughes, Bradley Wagenaar, Stephen Gloyd, Kemar Célestin, Marinho Elisma, Kesner Francois, Nancy Puttkammer

2020-Current year OA Pubs

OBJECTIVE: To evaluate and compare documentation completeness of HIV-related data by age group (children, adolescents and adults) in Haiti's Electronic Medical Record (EMR) system.

DESIGN: Cross-sectional evaluation.

SETTING: EMR data for 36 965 enrolment visits, and 123 608 return visits from 58 facilities in Haiti (from 2016 to 2022).

PARTICIPANTS: Children, adolescents and adults accessing HIV care and treatment services in Haiti.

MAIN EXPOSURE MEASURE: Health facility attendance for HIV-related healthcare.

MAIN OUTCOME MEASURE: Level of data completeness, as a measure of data quality. We developed Composite Completeness Scores (CCS scores) to measure data completeness. Lower scores meant lower completeness. …

A Combined Naturalistic Driving, Clinical, And Neurobehavioral Data Set For Investigating Aging And Dementia, Matthew Blake, David C Brown, Chen Chen, Noor Al-Hammadi, Ramon Casanova, Yiqi Zhu, Ganesh M Babulal

2020-Current year OA Pubs

Alzheimer's disease and related dementia (ADRD) are becoming increasingly prevalent and are predicted to affect up to 153 million globally by 2050. Outside of biomarkers that measure pathology, there is a lack of methods to quantify and study complex behaviors such as driving and managing finances that precede cognitive decline among older adults. The DRIVES Project at Washington University School of Medicine has developed a pipeline to measure naturalistic driving behavior of older adult drivers enrolled in longitudinal studies of aging and ADRD. This driving behavior is captured in the form of tabular data for each trip a participant takes …

The Senescence Associated Secretory Phenotype, A Key Marker Of Cellular Senescence, Is Elevated In Depression And Moderated By Sex, Nishika Navrange, Ana Paula Mendes-Silva, Charles F Reynolds, Julie Wetherell, Benoit Mulsant, Mary C Kimmel, Eric J Lenze, Breno Satler Diniz

2020-Current year OA Pubs

OBJECTIVE: Studies have found elevation in a key biomarker of aging (the senescence-associated secretory phenotype (SASP) index) in depression. We investigated whether sex moderates the association between the SASP and major depression in older adults.

METHODS: We included 423 older adults in a current major depressive episode and 140 adults with no history of depression. We measured the plasma levels of SASP biomarkers using multiplex immunoassays. The interaction effect between sex, depression diagnosis, and senescence markers were analyzed by general linear models, adjusted for confounding variables.

RESULTS: Individuals with depression had a higher SASP index than the healthy comparison group …

Establishment Of A Reverse Genetics System For Studying Human Immune Functions In Mice, Priya Pal, Shuai Gao, Hongbo Gao, Xiwen Qin, Marina Cella, Qiankun Wang, Liang Shan

2020-Current year OA Pubs

Reverse genetics approaches in mice are widely used to understand gene functions and their aberrations in diseases. However, limitations exist in translating findings from animal models to human physiology. Humanized mice provide a powerful bridge to understanding human physiology and mechanisms of disease pathogenesis while maintaining the feasibility of working with small animals. Methods for generating humanized mouse models that allow scientists to probe contributions of particular genes have been rudimentary. Here, we established an efficient method for generating genetically modified human cord blood-derived CD34

Networked Behaviors Associated With A Large-Scale Secure Messaging Network: Cross-Sectional Secondary Data Analysis, Laura Rosa Baratta, Linlin Xia, Daphne Lew, Elise Eiden, Y Jasmine Wu, Noshir Contractor, Bruce L Lambert, Sunny S Lou, Thomas Kannampallil

2020-Current year OA Pubs

BACKGROUND: Communication among health care professionals is essential for effective clinical care. Asynchronous text-based clinician communication-secure messaging-is rapidly becoming the preferred mode of communication. The use of secure messaging platforms across health care institutions creates large-scale communication networks that can be used to characterize how interaction structures affect the behaviors and outcomes of network members. However, the understanding of the structure and interactions within these networks is relatively limited.

OBJECTIVE: This study investigates the characteristics of a large-scale secure messaging network and its association with health care professional messaging behaviors.

METHODS: Data on electronic health record-integrated secure messaging use from …