Digital Commons Network^™

Multisensory Flicker Modulates Widespread Brain Networks And Reduces Interictal Epileptiform Discharges, Lou T Blanpain, Eric R Cole, Emily Chen, James K Park, Michael Y Walelign, Robert E Gross, Brian T Cabaniss, Jon T Willie, Annabelle C Singer

2020-Current year OA Pubs

Modulating brain oscillations has strong therapeutic potential. Interventions that both non-invasively modulate deep brain structures and are practical for chronic daily home use are desirable for a variety of therapeutic applications. Repetitive audio-visual stimulation, or sensory flicker, is an accessible approach that modulates hippocampus in mice, but its effects in humans are poorly defined. We therefore quantified the neurophysiological effects of flicker with high spatiotemporal resolution in patients with focal epilepsy who underwent intracranial seizure monitoring. In this interventional trial (NCT04188834) with a cross-over design, subjects underwent different frequencies of flicker stimulation in the same recording session with the effect …

Macromolecular Condensation Organizes Nucleolar Sub-Phases To Set Up A Ph Gradient, Matthew R King, Kiersten M Ruff, Andrew Z Lin, Avnika Pant, Mina Farag, Jared M Lalmansingh, Tingting Wu, Martin J Fossat, Wei Ouyang, Matthew D Lew, Emma Lundberg, Michael D Vahey, Rohit V Pappu

2020-Current year OA Pubs

Nucleoli are multicomponent condensates defined by coexisting sub-phases. We identified distinct intrinsically disordered regions (IDRs), including acidic (D/E) tracts and K-blocks interspersed by E-rich regions, as defining features of nucleolar proteins. We show that the localization preferences of nucleolar proteins are determined by their IDRs and the types of RNA or DNA binding domains they encompass. In vitro reconstitutions and studies in cells showed how condensation, which combines binding and complex coacervation of nucleolar components, contributes to nucleolar organization. D/E tracts of nucleolar proteins contribute to lowering the pH of co-condensates formed with nucleolar RNAs in vitro. In cells, this …

Chemotherapy Activates Inflammasomes To Cause Inflammation-Associated Bone Loss, Chun Wang, Khushpreet Kaur, Canxin Xu, Yousef Abu-Amer, Gabriel Mbalaviele

2020-Current year OA Pubs

Chemotherapy is a widely used treatment for a variety of solid and hematological malignancies. Despite its success in improving the survival rate of cancer patients, chemotherapy causes significant toxicity to multiple organs, including the skeleton, but the underlying mechanisms have yet to be elucidated. Using tumor-free mouse models, which are commonly used to assess direct off-target effects of anti-neoplastic therapies, we found that doxorubicin caused massive bone loss in wild-type mice, a phenotype associated with increased number of osteoclasts, leukopenia, elevated serum levels of danger-associated molecular patterns (DAMPs; e.g. cell-free DNA and ATP) and cytokines (e.g. IL-1β and IL-18). Accordingly, …

Pathophysiology Of Chikungunya Virus Infection Associated With Fatal Outcomes, William M De Souza, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors. The histopathologic, metabolite, and proteomic signatures of CHIK deaths reveal hemodynamic disorders and dysregulated immune responses. The CHIKV East-Central-South-African lineage …

Lung Type 3 Innate Lymphoid Cells Respond Early Following Mycobacterium Tuberculosis Infection, Shibali Das, Kuldeep Singh Chauhan, Mushtaq Ahmed, Sadia Akter, Lan Lu, Marco Colonna, Shabaana A Khader

2020-Current year OA Pubs

UNLABELLED: Tuberculosis is the leading cause of death due to an infectious disease worldwide. Innate lymphoid type 3 cells (ILC3s) mediate early protection during

IMPORTANCE: Tuberculosis is a leading cause of death due to a single infectious agent accounting for 1.6 million deaths each year. In our study, we determined the role of type 3 innate lymphoid cells in early immune events necessary for achieving protection during

Rare Genetic Variation In Fibronectin 1 (Fn1) Protects Against Apoeε4 In Alzheimer's Disease, Prabesh Bhattarai, Michael E Belloy, Et Al.

2020-Current year OA Pubs

The risk of developing Alzheimer's disease (AD) significantly increases in individuals carrying the APOEε4 allele. Elderly cognitively healthy individuals with APOEε4 also exist, suggesting the presence of cellular mechanisms that counteract the pathological effects of APOEε4; however, these mechanisms are unknown. We hypothesized that APOEε4 carriers without dementia might carry genetic variations that could protect them from developing APOEε4-mediated AD pathology. To test this, we leveraged whole-genome sequencing (WGS) data in the National Institute on Aging Alzheimer's Disease Family Based Study (NIA-AD FBS), Washington Heights/Inwood Columbia Aging Project (WHICAP), and Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA) cohorts and …

Transcription Factor C/Ebpα Is Required For The Development Of Ly6chi Monocytes But Not Ly6clo Monocytes, Sunkyung Kim, Jing Chen, Feiya Ou, Tian-Tian Liu, Suin Jo, William E Gillanders, Theresa L Murphy, Kenneth M Murphy

2020-Current year OA Pubs

Monocytes comprise two major subsets, Ly6C

Csf Biomarkers Of Immune Activation And Alzheimer's Disease For Predicting Cognitive Impairment Risk In The Elderly, Francis Shue, Rachel Hendrix, Jason Ulrich, Rachel L Henson, William Knight, Chengjie Xiong, Jigyasha Timsina, Yun Ju Sung, Carlos Cruchaga, David M Holtzman, Et Al.

2020-Current year OA Pubs

The immune system substantially influences age-related cognitive decline and Alzheimer's disease (AD) progression, affected by genetic and environmental factors. In a Mayo Clinic Study of Aging cohort, we examined how risk factors like APOE genotype, age, and sex affect inflammatory molecules and AD biomarkers in cerebrospinal fluid (CSF). Among cognitively unimpaired individuals over 65 (

Subcellular Pathways Through Vglut3-Expressing Mouse Amacrine Cells Provide Locally Tuned Object-Motion-Selective Signals In The Retina, Karl Friedrichsen, Jen-Chun Hsiang, Chin-I Lin, Liam Mccoy, Katia Valkova, Daniel Kerschensteiner, Josh L Morgan

2020-Current year OA Pubs

VGluT3-expressing mouse retinal amacrine cells (VG3s) respond to small-object motion and connect to multiple types of bipolar cells (inputs) and retinal ganglion cells (RGCs, outputs). Because these input and output connections are intermixed on the same dendrites, making sense of VG3 circuitry requires comparing the distribution of synapses across their arbors to the subcellular flow of signals. Here, we combine subcellular calcium imaging and electron microscopic connectomic reconstruction to analyze how VG3s integrate and transmit visual information. VG3s receive inputs from all nearby bipolar cell types but exhibit a strong preference for the fast type 3a bipolar cells. By comparing …

Blocking Senescence And Tolerogenic Function Of Dendritic Cells Induced By Γδ Treg Cells Enhances Tumor-Specific Immunity For Cancer Immunotherapy, Fusheng Si, Xia Liu, Yan Tao, Yuanqin Zhang, Feiya Ma, Eddy C Hsueh, Sidharth V Puram, Guangyong Peng

2020-Current year OA Pubs

BACKGROUND: Regulatory T (Treg) cells are a key component in maintaining the suppressive tumor microenvironment and immune suppression in different types of cancers. A precise understanding of the molecular mechanisms used by Treg cells for immune suppression is critical for the development of effective strategies for cancer immunotherapy.

METHODS: Senescence development and tolerogenic functions of dendritic cells (DCs) induced by breast cancer tumor-derived γδ Treg cells were fully characterized using real-time PCR, flow cytometry, western blot, and functional assays. Loss-of-function strategies with pharmacological inhibitor and/or neutralizing antibody were used to identify the potential molecule(s) and pathway(s) involved in DC senescence …

Vista Checkpoint Inhibition By Ph-Selective Antibody Sns-101 With Optimized Safety And Pharmacokinetic Profiles Enhances Pd-1 Response, Thomas Thisted, Yoshiko Takeuchi, Robert D Schreiber, Et Al.

2020-Current year OA Pubs

VISTA, an inhibitory myeloid-T-cell checkpoint, holds promise as a target for cancer immunotherapy. However, its effective targeting has been impeded by issues such as rapid clearance and cytokine release syndrome observed with previous VISTA antibodies. Here we demonstrate that SNS-101, a newly developed pH-selective VISTA antibody, addresses these challenges. Structural and biochemical analyses confirmed the pH-selectivity and unique epitope targeted by SNS-101. These properties confer favorable pharmacokinetic and safety profiles on SNS-101. In syngeneic tumor models utilizing human VISTA knock-in mice, SNS-101 shows in vivo efficacy when combined with a PD-1 inhibitor, modulates cytokine and chemokine signaling, and alters the …

Intestinal Cell Diversity And Treatment Responses In A Parasitic Nematode At Single Cell Resolution, Rahul Tyagi, Bruce A Rosa, Amanda Swain, Maxim N Artyomov, Douglas P Jasmer, Makedonka Mitreva

2020-Current year OA Pubs

BACKGROUND: Parasitic nematodes, significant pathogens for humans, animals, and plants, depend on diverse organ systems for intra-host survival. Understanding the cellular diversity and molecular variations underlying these functions holds promise for developing novel therapeutics, with specific emphasis on the neuromuscular system's functional diversity. The nematode intestine, crucial for anthelmintic therapies, exhibits diverse cellular phenotypes, and unraveling this diversity at the single-cell level is essential for advancing knowledge in anthelmintic research across various organ systems.

RESULTS: Here, using novel single-cell transcriptomics datasets, we delineate cellular diversity within the intestine of adult female Ascaris suum, a parasitic nematode species that infects animals …

A Compendium Of Multi-Omics Data Illuminating Host Responses To Lethal Human Virus Infections, Amie J Eisfeld, Larissa B Thackray, Qing Tan, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Human infections caused by viral pathogens trigger a complex gamut of host responses that limit disease, resolve infection, generate immunity, and contribute to severe disease or death. Here, we present experimental methods and multi-omics data capture approaches representing the global host response to infection generated from 45 individual experiments involving human viruses from the Orthomyxoviridae, Filoviridae, Flaviviridae, and Coronaviridae families. Analogous experimental designs were implemented across human or mouse host model systems, longitudinal samples were collected over defined time courses, and global multi-omics data (transcriptomics, proteomics, metabolomics, and lipidomics) were acquired by microarray, RNA sequencing, or mass spectrometry analyses. For …

Nfĸb Signaling Drives Myocardial Injury Via Ccr2+ Macrophages In A Preclinical Model Of Arrhythmogenic Cardiomyopathy, Stephen P. Chelko, Vinay R. Penna, Morgan Engel, Emily A. Shiel, Ann M. Centner, Waleed Farra, Elisa N. Cannon, Maicon Landim-Vieira, Niccole Schaible, Kory Lavine, Jeffrey E. Saffitz

2020-Current year OA Pubs

Nuclear factor κ-B (NFκB) is activated in iPSC-cardiac myocytes from patients with arrhythmogenic cardiomyopathy (ACM) under basal conditions, and inhibition of NFκB signaling prevents disease in Dsg2mut/mut mice, a robust mouse model of ACM. Here, we used genetic approaches and single-cell RNA-Seq to define the contributions of immune signaling in cardiac myocytes and macrophages in the natural progression of ACM using Dsg2mut/mut mice. We found that NFκB signaling in cardiac myocytes drives myocardial injury, contractile dysfunction, and arrhythmias in Dsg2mut/mut mice. NFκB signaling in cardiac myocytes mobilizes macrophages expressing C-C motif chemokine receptor-2 (CCR2+ cells) to affected areas within the …

Prevotella Copri And Microbiota Members Mediate The Beneficial Effects Of A Therapeutic Food For Malnutrition, Hao-Wei Chang, Evan M Lee, Yi Wang, Cyrus Zhou, Kali M Pruss, Suzanne Henrissat, Robert Y Chen, Clara Kao, Matthew C Hibberd, Hannah M Lynn, Daniel M Webber, Marie Crane, Jiye Cheng, Ye Chen, Jeffrey I Gordon, Et Al.

2020-Current year OA Pubs

Microbiota-directed complementary food (MDCF) formulations have been designed to repair the gut communities of malnourished children. A randomized controlled trial demonstrated that one formulation, MDCF-2, improved weight gain in malnourished Bangladeshi children compared to a more calorically dense standard nutritional intervention. Metagenome-assembled genomes from study participants revealed a correlation between ponderal growth and expression of MDCF-2 glycan utilization pathways by Prevotella copri strains. To test this correlation, here we use gnotobiotic mice colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains, with or without P. copri isolates closely matching the metagenome-assembled genomes. Combining gut metagenomics and metatranscriptomics …

Reliability And Validity Of Smartphone Cognitive Testing For Frontotemporal Lobar Degeneration, Adam M Staffaroni, Nupur Ghoshal, Jason Hassenstab, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Frontotemporal lobar degeneration (FTLD) is relatively rare, behavioral and motor symptoms increase travel burden, and standard neuropsychological tests are not sensitive to early-stage disease. Remote smartphone-based cognitive assessments could mitigate these barriers to trial recruitment and success, but no such tools are validated for FTLD.

OBJECTIVE: To evaluate the reliability and validity of smartphone-based cognitive measures for remote FTLD evaluations.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study conducted from January 10, 2019, to July 31, 2023, controls and participants with FTLD performed smartphone application (app)-based executive functioning tasks and an associative memory task 3 times over 2 weeks. …

A Targeted Proteomics Method For Quantifying Plasma Apolipoprotein Kinetics In Individual Mice Using Stable Isotope Labeling, Baohai Shao, Masami Shimizu-Albergine, Farah Kramer, Jenny E Kanter, Jay W Heinecke, Tomas Vaisar, Bettina Mittendorfer, Bruce W Patterson, Karin E Bornfeldt

2020-Current year OA Pubs

Altered apolipoprotein kinetics play a critical role in promoting dyslipidemia and atherogenesis. Human apolipoprotein kinetics have been extensively evaluated, but similar studies in mice are hampered by the lack of robust methods suitable for the small amounts of blood that can be collected at sequential time points from individual mice. We describe a targeted liquid chromatography tandem mass spectrometry method for simultaneously quantifying the stable isotope enrichment of several apolipoproteins represented by multiple peptides in serial blood samples (15 μl each) obtained after retro-orbital injection of

Changing Perceptions About The Dermatology Residency Application Process Among Applicants And Program Directors: 2020-2022, Fatuma-Ayaan B. Rinderknecht, Kandice C. Bailey, Danielle E. Novack, Adena E. Rosenblatt, Dana Dunleavy, Bobby D. Naemi, Ilana S. Rosman, Ammar Ahmed, Scott Worswick

2020-Current year OA Pubs

Importance Over the last two years, dermatology has undergone significant reforms in the residency application process in efforts to reduce applicant stress, increase equity, and due to the COVID-19 pandemic. Objective We aimed to determine applicant and program director (PD) perspectives in implementing these changes over the last two application cycles. Design, setting, and participants Anonymous online surveys were administered by the Association of American Medical Colleges (AAMC) to PDs and applicants from the 2021-2022 dermatology residency application cycle. These results were compared with similar online surveys distributed after the 2020-2021 cycle. Results Coordinated interview release was introduced in the …

Incidence And Mortality Of Covid-19-Associated Invasive Fungal Infections Among Critically Ill Intubated Patients: A Multicenter Retrospective Cohort Analysis, Julio C Zuniga-Moya, Benjamin Papadopoulos, Armaghan-E-Rehman Mansoor, Patrick B Mazi, Adriana M Rauseo, Andrej Spec

2020-Current year OA Pubs

BACKGROUND: An association between coronavirus disease 2019 (COVID-19)-associated invasive fungal infections (CAIFIs) and high mortality among intubated patients has been suggested in previous research. However, some of the current evidence was derived from small case series and multicenter studies conducted during different waves of the COVID-19 pandemic. We examined the incidence of CAIFIs and their associated mortality using a large, multicenter COVID-19 database built throughout the pandemic.

METHODS: We conducted a retrospective analysis of the National COVID Cohort Collaborative (N3C) database collected from 76 medical centers in the United States between January 2020 and August 2022. Patients were 18 years …

Cholesterol 25-Hydroxylase Mediates Neuroinflammation And Neurodegeneration In A Mouse Model Of Tauopathy, Danira Toral-Rios, Justin M Long, Jason D Ulrich, Jinsheng Yu, Michael R Strickland, Xianlin Han, David M Holtzman, Anil G Cashikar, Steven M Paul

2020-Current year OA Pubs

Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary tangles, in addition to neuroinflammation and changes in brain lipid metabolism. 25-Hydroxycholesterol (25-HC), a known modulator of both inflammation and lipid metabolism, is produced by cholesterol 25-hydroxylase encoded by Ch25h expressed as a "disease-associated microglia" signature gene. However, whether Ch25h influences tau-mediated neuroinflammation and neurodegeneration is unknown. Here, we show that in the absence of Ch25h and the resultant reduction in 25-HC, there is strikingly reduced age-dependent neurodegeneration and neuroinflammation in the hippocampus and entorhinal/piriform cortex of PS19 mice, which express the P301S mutant human tau transgene. Transcriptomic analyses of …

Adipose Tissue Peroxisomal Lipid Synthesis Orchestrates Obesity And Insulin Resistance Through Lxr-Dependent Lipogenesis, Brian Kleiboeker, Anyuan He, Min Tan, Dongliang Lu, Donghua Hu, Xuejing Liu, Parniyan Goodarzi, Fong-Fu Hsu, Babak Razani, Clay F Semenkovich, Irfan J Lodhi

2020-Current year OA Pubs

OBJECTIVE: Adipose tissue mass is maintained by a balance between lipolysis and lipid storage. The contribution of adipose tissue lipogenesis to fat mass, especially in the setting of high-fat feeding, is considered minor. Here we investigated the effect of adipose-specific inactivation of the peroxisomal lipid synthetic protein PexRAP on fatty acid synthase (FASN)-mediated lipogenesis and its impact on adiposity and metabolic homeostasis.

METHODS: To explore the role of PexRAP in adipose tissue, we metabolically phenotyped mice with adipose-specific knockout of PexRAP. Bulk RNA sequencing was used to determine transcriptomic responses to PexRAP deletion and

RESULTS: Adipose-specific PexRAP deletion promoted diet-induced …

Neutrophils Are Indispensable For Adverse Cardiac Remodeling In Heart Failure, Sergey Antipenko, Nicolas Mayfield, Miki Jinno, Matthias Gunzer, Mohamed Ameen Ismahil, Tariq Hamid, Sumanth D Prabhu, Gregg Rokosh

2020-Current year OA Pubs

Persistent immune activation contributes significantly to left ventricular (LV) dysfunction and adverse remodeling in heart failure (HF). In contrast to their well-known essential role in acute myocardial infarction (MI) as first responders that clear dead cells and facilitate subsequent reparative macrophage polarization, the role of neutrophils in the pathobiology of chronic ischemic HF is poorly defined. To determine the importance of neutrophils in the progression of ischemic cardiomyopathy, we measured their production, levels, and activation in a mouse model of chronic HF 8 weeks after permanent coronary artery ligation and large MI. In HF mice, neutrophils were more abundant both …

Brain High-Throughput Multi-Omics Data Reveal Molecular Heterogeneity In Alzheimer's Disease, Abdallah M. Eteleeb, Brenna C. Novotny, Carolina Soriano Tarraga, Christopher Sohn, Eliza Dhungel, Logan Brase, Aasritha Nallapu, Jared Buss, Fabiana Farias, Kristy Bergmann, Joseph Bradley, Joanne Norton, Jen Gentsch, Fengxian Wang, Albert A. Davis, John C. Morris, Celeste M. Karch, Richard J. Perrin, Bruno A. Benitez, Oscar Harari

2020-Current year OA Pubs

Unbiased data-driven omic approaches are revealing the molecular heterogeneity of Alzheimer disease. Here, we used machine learning approaches to integrate high-throughput transcriptomic, proteomic, metabolomic, and lipidomic profiles with clinical and neuropathological data from multiple human AD cohorts. We discovered 4 unique multimodal molecular profiles, one of them showing signs of poor cognitive function, a faster pace of disease progression, shorter survival with the disease, severe neurodegeneration and astrogliosis, and reduced levels of metabolomic profiles. We found this molecular profile to be present in multiple affected cortical regions associated with higher Braak tau scores and significant dysregulation of synapse-related genes, endocytosis, …

A Protective Role For Type I Interferon Signaling Following Infection With Mycobacterium Tuberculosis Carrying The Rifampicin Drug Resistance-Conferring Rpob Mutation H445y, Suhas Bobba, Kuldeep S. Chauhan, Sadia Akter, Shibali Das, Ekansh Mittal, Barun Mathema, Jennifer A. Philips, Shabaana A. Khader

2020-Current year OA Pubs

Interleukin-1 (IL-1) signaling is essential for controlling virulent Mycobacterium tuberculosis (Mtb) infection since antagonism of this pathway leads to exacerbated pathology and increased susceptibility. In contrast, the triggering of type I interferon (IFN) signaling is associated with the progression of tuberculosis (TB) disease and linked with negative regulation of IL-1 signaling. However, mice lacking IL-1 signaling can control Mtb infection if infected with an Mtb strain carrying the rifampin-resistance conferring mutation H445Y in its RNA polymerase β subunit (rpoB-H445Y Mtb). The mechanisms that govern protection in the absence of IL-1 signaling during rpoB-H445Y Mtb infection are unknown. In this study, …

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society Expert Consensus Statement On Catheter And Surgical Ablation Of Atrial Fibrillation, Stylianos Tzeis, Ralph J Damiano, Et Al.

2020-Current year OA Pubs

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a …

Comparative Lipidome Study Of Maternal Plasma, Milk, And Lamb Plasma In Sheep, Soundara Viveka Thangaraj, Adel Ghnenis, Brooke Pallas, Arpita Kalla Vyas, Brigid Gregg, Vasantha Padmanabhan

2020-Current year OA Pubs

Lipids play a critical role in neonate development and breastmilk is the newborn's major source of lipids. Milk lipids directly influence the neonate plasma lipid profile. The milk lipidome is dynamic, influenced by maternal factors and related to the maternal plasma lipidome. The close inter-relationship between the maternal plasma, milk and neonate plasma lipidomes is critical to understanding maternal-child health and nutrition. In this exploratory study, lipidomes of blood and breast milk from Suffolk sheep and matched lamb blood (n = 13), were profiled on day 34 post birth by untargeted mass spectrometry. Comparative multivariate analysis of the three matrices …

Fibrinolytic-Deficiencies Predispose Hosts To Septicemia From A Catheter-Associated Uti, Jonathan J Molina, Wei Xu, Karla Bergeron, Aleksandra Klim, Michael G Caparon, Scott J Hultgren, Alana Desai, Et Al.

2020-Current year OA Pubs

Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat partly due to development of multidrug-resistance from CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, here we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition …

Intergenerational Protective Anti-Gut Commensal Immunoglobulin G Originates In Early Life, Brigida Rusconi, Adina K Bard, Ryan Mcdonough, Angel M Kindsvogel, Jacqueline D Wang, Sreeram Udayan, Keely G Mcdonald, Rodney D Newberry, Phillip I Tarr

2020-Current year OA Pubs

Maternal immunoglobulins of the class G (IgGs) protect offspring from enteric infection, but when, where, and how these antibodies are physiologically generated and confer protection remains enigmatic. We found that circulating IgGs in adult mice preferentially bind early-life gut commensal bacteria over their own adult gut commensal bacteria. IgG-secreting plasma cells specific for early-life gut bacteria appear in the intestine soon after weaning, where they remain into adulthood. Manipulating exposure to gut bacteria or plasma cell development before, but not after, weaning reduced IgG-secreting plasma cells targeting early-life gut bacteria throughout life. Further, the development of this anti-gut commensal IgG …

Ly6c+ Monocytes In The Skin Promote Systemic Alphavirus Dissemination, Autumn C Holmes, Cormac J Lucas, Morgan E Brisse, Brian C Ware, Heather D Hickman, Thomas E Morrison, Michael S Diamond

2020-Current year OA Pubs

Alphaviruses are mosquito-transmitted pathogens that induce high levels of viremia, which facilitates dissemination and vector transmission. One prevailing paradigm is that, after skin inoculation, alphavirus-infected resident dendritic cells migrate to the draining lymph node (DLN), facilitating further rounds of infection and dissemination. Here, we assess the contribution of infiltrating myeloid cells to alphavirus spread. We observe two phases of virus transport to the DLN, one that occurs starting at 1 h post infection and precedes viral replication, and a second that requires replication in the skin, enabling transit to the bloodstream. Depletion of Ly6C

Pathogenic Variants In Crx Have Distinct Cis-Regulatory Effects On Enhancers And Silencers In Photoreceptors, James L Shepherdson, Ryan Z Friedman, Yiqiao Zheng, Chi Sun, Inez Y Oh, David M Granas, Barak A Cohen, Shiming Chen, Michael A White

2020-Current year OA Pubs

Dozens of variants in the gene for the homeodomain transcription factor (TF) cone-rod homeobox (