Medicine and Health Sciences Commons^™

Chromatin Conformation And Histone Modification Profiling Across Human Kidney Anatomic Regions, Haikuo Li, Dian Li, Benjamin D Humphreys

2020-Current year OA Pubs

The three major anatomic regions of the human kidney include the cortex, medulla and papilla, with different functions and vulnerabilities to kidney diseases. Epigenetic mechanisms underlying these anatomic structures are incompletely understood. Here, we performed chromatin conformation capture with Hi-C and histone modification H3K4me3/H3K27me3 Cleavage Under Targets and Release Using Nuclease (CUT&RUN) sequencing on the kidney cortex, medulla and papilla dissected from one individual donor. Nuclear suspensions were generated from each region and split subjected to paired Hi-C and CUT&RUN sequencing. We evaluated the quality of next-generation sequencing data, Hi-C chromatin contact matrices and CUT&RUN peak calling. H3K4me3 and H3K27me3 …

Mucosal Signatures Of Pathogenic T Cells In Hla-B*27+ Anterior Uveitis And Axial Spondyloarthritis, Michael A. Paley, Lynn M. Hassman, Grace L. Paley, Nicole Linskey, Ryan Agnew, Paulo Henrique Arantes De Faria, Annie Feng, Sophia Y. Li, Elisha D. O. Roberson, Philip A. Ruzycki, Ekaterina Esaulova, Jennifer Laurent, Lacey Feigl-Lenzen, Luke E. Springer, Chang Liu, Wayne M. Yokoyama, Et Al.

2020-Current year OA Pubs

HLA-B*27 was one of the first HLA alleles associated with an autoimmune disease, i.e., axial spondyloarthritis (axSpA) and acute anterior uveitis (B27AAU), which cause joint and eye inflammation, respectively. Gastrointestinal inflammation has been suggested as a trigger of axSpA. We recently identified a bacterial peptide (YeiH) that can be presented by HLA-B*27 to expanded public T cell receptors in the joint in axSpA and the eye in B27AAU. While YeiH is present in enteric microbiota and pathogens, additional evidence that pathogenic T cells in HLA-B*27-associated autoimmunity may have had a prior antigenic encounter within the gastrointestinal tract remains lacking. Here, …

Cellular Endosomal Potassium Ion Flux Regulates Arenavirus Uncoating During Virus Entry, Amelia B Shaw, Hiu Nam Tse, Owen Byford, Grace Plahe, Alex Moon-Walker, Samantha E Hover, Erica Ollmann Saphire, Sean P J Whelan, Jamel Mankouri, Juan Fontana, John N Barr

2020-Current year OA Pubs

Lymphocytic choriomeningitis virus (LCMV) is an enveloped and segmented negative-sense RNA virus classified within the

Terahertz Tunable Three-Dimensional Photonic Jets, Behrooz Rezaei, Babak Yahyapour, Arash Darafsheh

2020-Current year OA Pubs

Highly localized electromagnetic field distributions near the "shadow-side" surface of certain transparent mesoscale bodies illuminated by light waves are called photonic jets. We demonstrated formation of three-dimensional (3D) tunable photonic jets in terahertz regime (terajets, TJs) by dielectric micro-objects -including spheres, cylinders, and cubes-coated with a bulk Dirac semimetal (BDS) layer, under uniform beam illumination. The optical characteristics of the produced TJs can be modulated dynamically through tuning the BDS layer's index of refraction via changing its Fermi energy. It is demonstrated that the Fermi energy of BDS layer has a significant impact on tuning the optical characteristics of the …

Spanish Translation Of The Expert Recommendations For Implementing Change (Eric) Compilation, Amelia E Van Pelt, Alejandra Paniagua-Avila, Amanda Sanchez, Stephanie Sila, Elizabeth D Lowenthal, Byron J Powell, Rinad S Beidas

2020-Current year OA Pubs

BACKGROUND: Most implementation science resources (e.g., taxonomies) are published in English. Linguistic inaccessibility creates a barrier to the conduct of implementation research among non-English-speaking populations, so translation of resources is needed. Translation into Spanish can facilitate widespread reach, given the large proportion of Spanish speakers around the world. This research aimed to systematically translate the Expert Recommendations for Implementation Change (ERIC) compilation into Spanish as an exemplar for the linguistic translation process.

METHODS: Using the World Health Organization guidelines, this work translated the ERIC compilation strategy names, short definitions, and thematic clusters through a three-step process: 1) forward translation into …

Brilacidin, A Novel Antifungal Agent Against Cryptococcus Neoformans, Camila Diehl, Dong-Gyu Kim, Tamara L Doering, Et Al.

2020-Current year OA Pubs

UNLABELLED:

IMPORTANCE: Invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Cryptococcosis, one of the most prevalent fungal diseases, is generally characterized by meningitis and is mainly caused by two closely related species of basidiomycetous yeasts,

A Reinterpretation Of The Relationship Between Persistent And Resurgent Sodium Currents, Samuel P Brown, Ryan J Lawson, Jonathan D Moreno, Joseph L Ransdell

2020-Current year OA Pubs

The resurgent sodium current (I

Development Of A Hydrogen Peroxide-Inactivated Vaccine That Protects Against Viscerotropic Yellow Fever In A Non-Human Primate Model, Ian J Amanna, Archana Thomas, Flora Engelmann, Erika Hammarlund, Hans-Peter Raué, Adam L Bailey, Elizabeth A Poore, Benjamin K Quintel, Anne D Lewis, Michael K Axthelm, Amanda L Johnson, Lois M A Colgin, Michael S Diamond, Ilhem Messaoudi, Mark K Slifka

2020-Current year OA Pubs

Yellow fever virus (YFV) is endemic in >40 countries and causes viscerotropic disease with up to 20%-60% mortality. Successful live-attenuated yellow fever (YF) vaccines were developed in the mid-1930s, but their use is restricted or formally contraindicated in vulnerable populations including infants, the elderly, and people with compromised immune systems. In these studies, we describe the development of a next-generation hydrogen peroxide-inactivated YF vaccine and determine immune correlates of protection based on log neutralizing index (LNI) and neutralizing titer-50% (NT

Early Bolus Epinephrine Administration During Pediatric Cardiopulmonary Resuscitation For Bradycardia With Poor Perfusion: An Icu-Resuscitation Study, Amanda J O'Halloran, Stuart H Friess, Arushi Manga, Et Al.

2020-Current year OA Pubs

BACKGROUND: Half of pediatric in-hospital cardiopulmonary resuscitation (CPR) events have an initial rhythm of non-pulseless bradycardia with poor perfusion. Our study objectives were to leverage granular data from the ICU-RESUScitation (ICU-RESUS) trial to: (1) determine the association of early epinephrine administration with survival outcomes in children receiving CPR for bradycardia with poor perfusion; and (2) describe the incidence and time course of the development of pulselessness.

METHODS: Prespecified secondary analysis of ICU-RESUS, a multicenter cluster randomized trial of children (<  19 years) receiving CPR in 18 intensive care units in the United States. Index events (October 2016-March 2021) lasting ≥ 2 min with a documented initial rhythm of bradycardia with poor perfusion were included. Associations between early epinephrine (first 2 min of CPR) and outcomes were evaluated with Poisson multivariable regression controlling for a priori pre-arrest characteristics. Among patients with arterial lines, intra-arrest blood pressure waveforms were reviewed to determine presence of a pulse during CPR interruptions. The temporal nature of progression to pulselessness was described and outcomes were compared between patients according to subsequent pulselessness status.

RESULTS: Of 452 eligible subjects, 322 (71%) received early epinephrine. The early epinephrine group had higher pre-arrest severity of illness …

Exploring Lipin1 As A Promising Therapeutic Target For The Treatment Of Duchenne Muscular Dystrophy, Abdulrahman Jama, Abdullah A Alshudukhi, Steve Burke, Lixin Dong, John Karanja Kamau, Brooklyn Morris, Ibrahim A Alkhomsi, Brian N Finck, Andrew Alvin Voss, Hongmei Ren

2020-Current year OA Pubs

BACKGROUND: Duchenne muscular dystrophy (DMD) is a progressive and devastating muscle disease, resulting from the absence of dystrophin. This leads to cell membrane instability, susceptibility to contraction-induced muscle damage, subsequent muscle degeneration, and eventually disability and early death of patients. Currently, there is no cure for DMD. Our recent studies identified that lipin1 plays a critical role in maintaining myofiber stability and integrity. However, lipin1 gene expression levels are dramatically reduced in the skeletal muscles of DMD patients and mdx mice.

METHODS: To identify whether increased lipin1 expression could prevent dystrophic pathology, we employed unique muscle-specific mdx:lipin1 transgenic (mdx:lipin1

RESULTS: …

Mate Selection And Current Trends In The Prevalence Of Autism, Elizabeth Forsen, Natasha Marrus, Jacqueline Joyce, Yi Zhang, John N Constantino

2020-Current year OA Pubs

BACKGROUND: According to the most recent U.S. CDC surveillance data, the rise in prevalence of childhood autism spectrum disorder among minority children has begun to outpace that of non-Hispanic white children. Since prior research has identified possible differences in the extent of mate selection for autistic traits across families of different ethnicity, this study examined variation in autism related traits in contemporaneous, epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white populations. The purpose was to determine whether discrepancies by ethnicity could contribute to differential increases in prevalence in the current generation of young children.

METHODS: Birth records …

Chimeric Viruses Enable Study Of Antibody Responses To Human Rotaviruses In Mice, Sarah Woodyear, Tawny L Chandler, Takahiro Kawagishi, Tom M Lonergan, Vanshika A Patel, Caitlin A Williams, Sallie R Permar, Siyuan Ding, Sarah L Caddy

2020-Current year OA Pubs

The leading cause of gastroenteritis in children under the age of five is rotavirus infection, accounting for 37% of diarrhoeal deaths in infants and young children globally. Oral rotavirus vaccines have been widely incorporated into national immunisation programs, but whilst these vaccines have excellent efficacy in high-income countries, they protect less than 50% of vaccinated individuals in low- and middle-income countries. In order to facilitate the development of improved vaccine strategies, a greater understanding of the immune response to existing vaccines is urgently needed. However, the use of mouse models to study immune responses to human rotavirus strains is currently …

Papillary Tumor Of The Pineal Region: Analysis Of Dna Methylation Profiles And Clinical Outcomes In 76 Cases, Zhichao Wu, Sonika Dahiya, Et Al.

2020-Current year OA Pubs

Papillary tumor of the pineal region (PTPR) is an uncommon tumor of the pineal region with distinctive histopathologic and molecular characteristics. Experience is limited with respect to its molecular heterogeneity and clinical characteristics. Here, we describe 39 new cases and combine these with 37 previously published cases for a cohort of 76 PTPR's, all confirmed by methylation profiling. As previously reported, two main methylation groups were identified (PTPR-A and PTPR-B). In our analysis we extended the subtyping into three subtypes: PTPR-A, PTPR-B1 and PTPR-B2 supported by DNA methylation profile and genomic copy number variations. Frequent loss of chromosome 3 or …

Social Vulnerability And Surgery Outcomes: A Cross-Sectional Analysis, Mohamed Abdelhack Washington University School Of Medicine In St. Louis, Sandhya Tripathi, Yixin Chen, Michael S Avidan, Christopher R King

2020-Current year OA Pubs

BACKGROUND: Post-operative complications present a challenge to the healthcare system due to the high unpredictability of their incidence. Socioeconomic conditions have been established as social determinants of health. However, their contribution relating to postoperative complications is still unclear as it can be heterogeneous based on community, type of surgical services, and sex and gender. Uncovering these relations can enable improved public health policy to reduce such complications.

METHODS: In this study, we conducted a large population cross-sectional analysis of social vulnerability and the odds of various post-surgical complications. We collected electronic health records data from over 50,000 surgeries that happened …

Improving Hypertension Control In Nigeria: Early Policy Implications From The Hypertension Treatment In Nigeria Program, Oluwabunmi Ogungbe, Chibuzor Abasilim, Mark D Huffman, Dike Ojji, Hypertension Treatment In Nigeria Program Team

2020-Current year OA Pubs

Hypertension poses a significant health burden globally. In Nigeria, hypertension prevalence is on the rise, with low rates of awareness, treatment, and control. This policy brief explores the critical gaps addressed by the Hypertension Treatment in Nigeria (HTN) Program, highlighting its strengths, initial outcomes, and scalability in primary care settings. The HTN Program employs an integrated, multilevel care model based on the World Health Organization's HEARTS technical package, including patient registration and empanelment, team-based care, training and supervision, a standardized treatment protocol, a health information management system, and a drug revolving fund to improve medication accessibility. By December 2023, hypertension …

Early Depletion Of Gut Microbiota Shape Oligodendrocyte Response After Traumatic Brain Injury, Kirill Shumilov, Allen Ni, Maria Garcia-Bonilla, Marta Celorrio, Stuart H Friess

2020-Current year OA Pubs

BACKGROUND: This study is a cost-effectiveness study of two implementation strategies designed to train therapists in college and university counseling centers to deliver interpersonal psychotherapy. Costs of implementing a train-the-trainer (TTT) strategy versus an expert consultation strategy were estimated, and their relative effects upon therapist outcomes were calculated and compared.

METHODS: Twenty four counseling centers were recruited across the United States. These centers were randomized to either a TTT (experimental) condition, in which an in-house therapist trained other center therapists, or an expert consultation condition, in which center therapists participated in a workshop and received 12 months of ongoing supervision. …

Electroencephalogram Alpha Oscillations In Stroke Recovery: Insights Into Neural Mechanisms From Combined Transcranial Direct Current Stimulation And Mirror Therapy In Relation To Activities Of Daily Life, Chia-Lun Liu, Ya-Wen Tu, Ming-Wei Li, Ku-Chou Chang, Chih-Hung Chang, Chih-Kuang Chen, Ching-Yi Wu

2020-Current year OA Pubs

The goal of stroke rehabilitation is to establish a robust protocol for patients to live independently in community. Firstly, we examined the impact of 3 hybridized transcranial direct current stimulation (tDCS)-mirror therapy interventions on activities of daily life (ADL) in stroke patients. Secondly, we explored the underlying therapeutic mechanisms with theory-driven electroencephalography (EEG) indexes in the alpha band. This was achieved by identifying the unique contributions of alpha power in motor production to ADL in relation to the premotor cortex (PMC), primary cortex (M1), and Sham tDCS with mirror therapy. The results showed that, although post-intervention ADL improvement was comparable …

Adapting An Intervention To Address Barriers To Pain Management In Hospice: Formative Research To Inform Empower-D For Dementia Caregivers, Karla T Washington, Morgan L Van Vleck, Todd D Becker, George Demiris, Debra Parker Oliver, Paul E Tatum, Jacquelyn J Benson, John G Cagle

2020-Current year OA Pubs

BACKGROUND: Nearly half of more than 1.7 million older Americans who receive hospice care each year have a primary or comorbid diagnosis of dementia. Pain is often undertreated in this patient population owing to myriad factors, including unmet informational needs among family caregivers.

OBJECTIVE: We sought to inform the adaptation of a pain education intervention for hospice family caregivers to the context of dementia by eliciting feedback on the educational content covered in adapted intervention materials.

DESIGN: We conducted a multimethod, formative research study to inform the adaptation of an existing, evidence-based intervention.

SETTING/SUBJECTS: The study included a purposively recruited …

A Hybrid Epithelial/Mesenchymal State In Head And Neck Cancer: A Biomarker For Survival With Differential Prognosis By Self-Reported Race, Angela L Mazul, Thomas F Barrett, Graham Colditz, Anuraag S Parikh, Salma Ramadan, Jose P Zevallos, Jason T Rich, R Alex Harbison, Ryan S Jackson, Patrik Pipkorn, Paul Zolkind, Itay Tirosh, Sidharth V Puram

2020-Current year OA Pubs

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the 6

METHODS: Given the overlap in gene expression between hybrid E/M malignant cells and cancer-associated fibroblasts, we utilized deconvolution of bulk RNA sequencing data from oral cavity and laryngeal squamous cell carcinoma tumors from The Cancer Genome Atlas. We utilized our previously collected single-cell profiles to generate inferred malignant profiles and then scored these for hybrid E/M. We then conducted a survival analysis on overall and disease-free survival among self-reported Black and White Americans.

FINDINGS: The hybrid E/M state was differentially associated with head and neck cancer survival by self-reported …

Genetic And Multi-Omic Resources For Alzheimer Disease And Related Dementia From The Knight Alzheimer Disease Research Center, Maria Victoria Fernandez, Menghan Liu, Aleksandra Beric, Matt Johnson, Arda Cetin, Maulik Patel, John Budde, Pat Kohlfeld, Kristy Bergmann, Joseph Lowery, Allison Flynn, William Brock, Brenda Sanchez Montejo, Jen Gentsch, Nicholas Sykora, Joanne Norton, Jen Gentsch, Olga Valdez, Priyanka Gorijala, Jessie Sanford, Yichen Sun, Ciyang Wang, Dan Western, Jigyasha Timsina, Tassia Mangetti Goncalves, Anh N Do, Yun Ju Sung, Guoyan Zhao, John C Morris, Krista Moulder, David M Holtzman, Randall J Bateman, Celeste Karch, Jason Hassenstab, Chengjie Xiong, Suzanne E Schindler, Joyce Joy Balls-Berry, Tammie L S Benzinger, Richard J Perrin, Andrea Denny, B Joy Snider, Susan L Stark, Laura Ibanez, Carlos Cruchaga

2020-Current year OA Pubs

The Knight-Alzheimer Disease Research Center (Knight-ADRC) at Washington University in St. Louis has pioneered and led worldwide seminal studies that have expanded our clinical, social, pathological, and molecular understanding of Alzheimer Disease. Over more than 40 years, research volunteers have been recruited to participate in cognitive, neuropsychologic, imaging, fluid biomarkers, genomic and multi-omic studies. Tissue and longitudinal data collected to foster, facilitate, and support research on dementia and aging. The Genetics and high throughput -omics core (GHTO) have collected of more than 26,000 biological samples from 6,625 Knight-ADRC participants. Samples available include longitudinal DNA, RNA, non-fasted plasma, cerebrospinal fluid pellets, …

Pulmonary Osteoclast-Like Cells In Silica Induced Pulmonary Fibrosis, Yoshihiro Hasegawa, Steven L Teitelbaum, Et Al.

2020-Current year OA Pubs

The pathophysiology of silicosis is poorly understood, limiting development of therapies for those who have been exposed to the respirable particle. We explored mechanisms of silica-induced pulmonary fibrosis in human lung samples collected from patients with occupational exposure to silica and in a longitudinal mouse model of silicosis using multiple modalities including whole-lung single-cell RNA sequencing and histological, biochemical, and physiologic assessments. In addition to pulmonary inflammation and fibrosis, intratracheal silica challenge induced osteoclast-like differentiation of alveolar macrophages and recruited monocytes, driven by induction of the osteoclastogenic cytokine, receptor activator of nuclear factor κΒ ligand (RANKL) in pulmonary lymphocytes, and …

Thermodynamic Coupling Of The Tandem Rrm Domains Of Hnrnp A1 Underlie Its Pleiotropic Rna Binding Functions, Jeffrey D Levengood, Davit Potoyan, Srinivasa Penumutchu, Abhishek Kumar, Qianzi Zhou, Yiqing Wang, Alexandar L Hansen, Sebla Kutluay, Julien Roche, Blanton S Tolbert

2020-Current year OA Pubs

The functional properties of RNA binding proteins (RBPs) require allosteric regulation through interdomain communication. Despite the importance of allostery to biological regulation, only a few studies have been conducted to describe the biophysical nature by which interdomain communication manifests in RBPs. Here, we show for hnRNP A1 that interdomain communication is vital for the unique stability of its amino-terminal domain, which consists of two RNA recognition motifs (RRMs). These RRMs exhibit drastically different stability under pressure. RRM2 unfolds as an individual domain but remains stable when appended to RRM1. Variants that disrupt interdomain communication between the tandem RRMs show a …

Genome-Wide Analyses Reveal A Potential Role For The Mapt, Mobp, And Apoe Loci In Sporadic Frontotemporal Dementia, Claudia Manzoni, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10

Dual-Localized Pptc7 Limits Mitophagy Through Proximal And Dynamic Interactions With Bnip3 And Nix, Lianjie Wei, Mehmet Oguz Gok, Jordyn D Svoboda, Keri-Lyn Kozul, Merima Forny, Jonathan R Friedman, Natalie M Niemi

2020-Current year OA Pubs

PPTC7 is a mitochondrial-localized phosphatase that suppresses BNIP3- and NIX-mediated mitophagy, but the mechanisms underlying this regulation remain ill-defined. Here, we demonstrate that loss of PPTC7 upregulates BNIP3 and NIX post-transcriptionally and independent of HIF-1α stabilization. Loss of PPTC7 prolongs the half-life of BNIP3 and NIX while blunting their accumulation in response to proteasomal inhibition, suggesting that PPTC7 promotes the ubiquitin-mediated turnover of BNIP3 and NIX. Consistently, overexpression of PPTC7 limits the accumulation of BNIP3 and NIX protein levels, which requires an intact catalytic motif but is surprisingly independent of its targeting to mitochondria. Consistently, we find that PPTC7 is …

Complications And Health-Related Quality Of Life In Children With Various Etiologies Of Early-Onset Scoliosis Treated With Magnetically Controlled Growing Rods- A Multicenter Study, Pawel Glowka, Pawel Grabala, Munish C Gupta, Daniel E Pereira, Michal Latalski, Anna Danielewicz, Michal Grabala, Marek Tomaszewski, Tomasz Kotwicki

2020-Current year OA Pubs

No abstract provided.

Phase Ib Study Of Unesbulin (Ptc596) Plus Dacarbazine For The Treatment Of Locally Recurrent, Unresectable Or Metastatic, Relapsed Or Refractory Leiomyosarcoma, Brian A Van Tine, Matthew A Ingham, Steven Attia, Christian F Meyer, John D Baird, Esther Brooks-Asplund, Dhiren D'Silva, Ronald Kong, Anthony Mwatha, Kylie O'Keefe, Marla Weetall, Robert Spiegel, Gary K Schwartz

2020-Current year OA Pubs

PURPOSE: This multicenter, single-arm, open-label, phase Ib study was designed to determine the recommended phase II dose (RP2D) and to evaluate the safety and preliminary efficacy of unesbulin plus dacarbazine (DTIC) in patients with advanced leiomyosarcoma (LMS).

PATIENTS AND METHODS: Adult subjects with locally advanced, unresectable or metastatic, relapsed or refractory LMS were treated with escalating doses of unesbulin orally twice per week in combination with DTIC 1,000 mg/m

RESULTS: Unesbulin 300 mg administered orally twice per week in combination with DTIC 1,000 mg/m

CONCLUSION: Unesbulin 300 mg twice per week plus DTIC 1,000 mg/m

Hemodynamics Regulate Spatiotemporal Artery Muscularization In The Developing Circle Of Willis, Siyuan Cheng, Ivan Fan Xia, Renate Wanner, Javier Abello, Amber N Stratman, Stefania Nicoli

2020-Current year OA Pubs

Vascular smooth muscle cells (VSMCs) envelop vertebrate brain arteries and play a crucial role in regulating cerebral blood flow and neurovascular coupling. The dedifferentiation of VSMCs is implicated in cerebrovascular disease and neurodegeneration. Despite its importance, the process of VSMC differentiation on brain arteries during development remains inadequately characterized. Understanding this process could aid in reprogramming and regenerating dedifferentiated VSMCs in cerebrovascular diseases. In this study, we investigated VSMC differentiation on zebrafish circle of Willis (CoW), comprising major arteries that supply blood to the vertebrate brain. We observed that arterial specification of CoW endothelial cells (ECs) occurs after their migration …

Displace Study Shows Poor Quality Of Transcranial Doppler Ultrasound For Stroke Risk Screening In Sickle Cell Anemia, Kimberly A Davidow, Robin E Miller, Shannon M Phillips, Alyssa M Schlenz, Martina Mueller, Monica L Hulbert, Lewis L Hsu, Neha Bhasin, Robert J Adams, Julie Kanter

2020-Current year OA Pubs

Children with sickle cell anemia (SCA) are at increased risk of stroke when compared with their age-based counterparts. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) previously demonstrated that with the use of transcranial Doppler ultrasound (TCD; Sickle Stroke Screen) and chronic red cell transfusion, the risk of stroke is reduced by over 90%. The STOP criteria detailed the type and method of measurement required; the time-averaged mean maximum velocity (TAMMV). Unfortunately, it has been difficult to adhere to the appropriate TAMMV measurements. The objectives of this study were to assess the quality of TCD and transcranial Doppler imaging …

Progenitors Of Distinct Lineages Shape The Diversity Of Mature Type 2 Conventional Dendritic Cells, Patrick Fernandes Rodrigues, Tihana Trsan, Grozdan Cvijetic, Darya Khantakova, Santosh K Panda, Zhaoyuan Liu, Florent Ginhoux, Marina Cella, Marco Colonna

2020-Current year OA Pubs

Conventional dendritic cells (cDC) are antigen-presenting cells comprising cDC1 and cDC2, responsible for priming naive CD8

Cxcl16-Dependent Scavenging Of Oxidized Lipids By Islet Macrophages Promotes Differentiation Of Pathogenic Cd8+ T Cells In Diabetic Autoimmunity, Neetu Srivastava, Hao Hu, Orion J Peterson, Anthony N Vomund, Marta Stremska, Mohammad Zaman, Shilpi Giri, Tiandao Li, Cheryl F Lichti, Pavel N Zakharov, Bo Zhang, Nada A Abumrad, Yi-Guang Chen, Kodi S Ravichandran, Emil R Unanue, Xiaoxiao Wan

2020-Current year OA Pubs

The pancreatic islet microenvironment is highly oxidative, rendering β cells vulnerable to autoinflammatory insults. Here, we examined the role of islet resident macrophages in the autoimmune attack that initiates type 1 diabetes. Islet macrophages highly expressed CXCL16, a chemokine and scavenger receptor for oxidized low-density lipoproteins (OxLDLs), regardless of autoimmune predisposition. Deletion of Cxcl16 in nonobese diabetic (NOD) mice suppressed the development of autoimmune diabetes. Mechanistically, Cxcl16 deficiency impaired clearance of OxLDL by islet macrophages, leading to OxLDL accumulation in pancreatic islets and a substantial reduction in intra-islet transitory (Tex