Digital Commons Network^™

Novel Vaccine Against Pathological Pyroglutamate-Modified Amyloid Beta For Prevention Of Alzheimer's Disease, Karen Zagorski, Olga King, Armine Hovakimyan, Irina Petrushina, Tatevik Antonyan, Gor Chailyan, Manush Ghazaryan, Krzysztof L Hyrc, Jean Paul Chadarevian, Hayk Davtyan, Mathew Blurton-Jones, David H Cribbs, Michael G Agadjanyan, Anahit Ghochikyan

2020-Current year OA Pubs

Post-translationally modified N-terminally truncated amyloid beta peptide with a cyclized form of glutamate at position 3 (pE

Sustained Alternate-Day Fasting Potentiates Doxorubicin Cardiotoxicity, Mualla Ozcan, Zhen Guo, Carla Valenzuela Ripoll, Ahmed Diab, Antonino Picataggi, David Rawnsley, Aynaz Lotfinaghsh, Carmen Bergom, Jeff Szymanski, Daniel Hwang, Jie Zheng, Robert J Hayashi, Pamela K Woodard, Attila Kovacs, Joel Schilling, Babak Razani, Abhinav Diwan, Ali Javaheri, Et Al.

2020-Current year OA Pubs

Fasting strategies are under active clinical investigation in patients receiving chemotherapy. Prior murine studies suggest that alternate-day fasting may attenuate doxorubicin cardiotoxicity and stimulate nuclear translocation of transcription factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis. In this study, human heart tissue from patients with doxorubicin-induced heart failure demonstrated increased nuclear TFEB protein. In mice treated with doxorubicin, alternate-day fasting or viral TFEB transduction increased mortality and impaired cardiac function. Mice randomized to alternate-day fasting plus doxorubicin exhibited increased TFEB nuclear translocation in the myocardium. When combined with doxorubicin, cardiomyocyte-specific TFEB overexpression provoked cardiac remodeling, while systemic …

Inequities In Treatments And Outcomes Among Patients Hospitalized With Hypertrophic Cardiomyopathy In The United States, Daniel Y Johnson, R J Waken, Daniel K Fox, Gmerice Hammond, Karen E Joynt Maddox, Sharon Cresci

2020-Current year OA Pubs

Background Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiac disease. In small studies, sociodemographic factors have been associated with disparities in septal reduction therapy, but little is known about the association of sociodemographic factors with HCM treatments and outcomes more broadly. Methods and Results Using the National Inpatient Survey from 2012 to 2018, HCM diagnoses and procedures were identified by

Connective Tissue Presentation In Two Families Expands The Phenotypic Spectrum Of Pyroxd1 Disorders, Frances J Evesson, Gregory Dziaduch, Samantha J Bryen, Francesca Moore, Sara Pittman, Beena Devanapalli, Leigh B Waddell, Monique M Ryan, Manoj P Menezes, Conrad C Weihl, Adviye Ayper Tolun, Craig Zaidman, Helen Young, Lesley C Adès, Sandra T Cooper

2020-Current year OA Pubs

Recessive variants in the oxidoreductase PYROXD1 are reported to cause a myopathy in 22 affected individuals from 15 families. Here, we describe two female probands from unrelated families presenting with features of a congenital connective tissue disorder including osteopenia, blue sclera, soft skin, joint hypermobility and neuromuscular junction dysfunction in addition to known features of PYROXD1 myopathy including respiratory difficulties, weakness, hypotonia and oromotor dysfunction. Proband AII:1 is compound heterozygous for the recurrent PYROXD1 variant Chr12(GRCh38):g.21452130A>G;NM_024854.5:c.464A>G;p.(N155S) and Chr12(GRCh38):g.21462019_21462022del;NM_024854.5:c.892_895del;p.(V298Mfs*4) and proband BII:1 is compound heterozygous for Chr12(GRCh38):g.21468739-21468741del;NM_024854.5:c.1488_1490del;p.(E496del) and Chr12(GRCh38):g.21467619del;NM_024854.5:c.1254+1del. RNA studies demonstrate c.892_895del;p.(V298Mfs*4) is targeted by nonsense mediated decay …

Stromal And Therapy-Induced Macrophage Proliferation Promotes Pdac Progression And Susceptibility To Innate Immunotherapy, Chong Zuo, John M Baer, Brett L Knolhoff, Jad I Belle, Xiuting Liu, Angela Alarcon De La Lastra, Graham D Hogg, Natalie L Kingston, Marcus A Breden, Paarth B Dodhiawala, Daniel Cui Zhou, Varintra E Lander, C Alston James, Li Ding, Kian-Huat Lim, Ryan C Fields, William G Hawkins, Jason D Weber, Guoyan Zhao, David G Denardo, Et Al.

2020-Current year OA Pubs

Tumor-associated macrophages (TAMs) are abundant in pancreatic ductal adenocarcinomas (PDACs). While TAMs are known to proliferate in cancer tissues, the impact of this on macrophage phenotype and disease progression is poorly understood. We showed that in PDAC, proliferation of TAMs could be driven by colony stimulating factor-1 (CSF1) produced by cancer-associated fibroblasts. CSF1 induced high levels of p21 in macrophages, which regulated both TAM proliferation and phenotype. TAMs in human and mouse PDACs with high levels of p21 had more inflammatory and immunosuppressive phenotypes. p21 expression in TAMs was induced by both stromal interaction and/or chemotherapy treatment. Finally, by modeling …

Intrinsic Tgf-Β Signaling Attenuates Proximal Tubule Mitochondrial Injury And Inflammation In Chronic Kidney Disease, Merve Kayhan, Judith Vouillamoz, Daymé Gonzalez Rodriguez, Milica Bugarski, Yasutaka Mitamura, Julia Gschwend, Christoph Schneider, Andrew Hall, David Legouis, Cezmi A Akdis, Leary Peter, Hubert Rehrauer, Leslie Gewin, Roland H Wenger, Stellor Nlandu Khodo

2020-Current year OA Pubs

Excessive TGF-β signaling and mitochondrial dysfunction fuel chronic kidney disease (CKD) progression. However, inhibiting TGF-β failed to impede CKD in humans. The proximal tubule (PT), the most vulnerable renal segment, is packed with giant mitochondria and injured PT is pivotal in CKD progression. How TGF-β signaling affects PT mitochondria in CKD remained unknown. Here, we combine spatial transcriptomics and bulk RNAseq with biochemical analyses to depict the role of TGF-β signaling on PT mitochondrial homeostasis and tubulo-interstitial interactions in CKD. Male mice carrying specific deletion of Tgfbr2 in the PT have increased mitochondrial injury and exacerbated Th1 immune response in …

Clinical Characteristics And Treatment Patterns Of Pregnant Women With Hypertension In Primary Care In The Federal Capital Territory Of Nigeria: Cross-Sectional Results From The Hypertension Treatment In Nigeria Program, Zainab Mahmoud, Ikechukwu A Orji, Gabriel L Shedul, Kasarachi Aluka-Omitiran, Nanna Ripiye, Blessing Akor, Helen Eze, Tunde Ojo, Guhan Iyer, Abigail S Baldridge, Lisa R Hirschhorn, Mark D Huffman, Dike B Ojji

2020-Current year OA Pubs

BACKGROUND: Hypertensive disorders of pregnancy, including hypertension, are a leading cause of maternal mortality in Nigeria. However, there is a paucity of data on pregnant women with hypertension who receive care in primary health care facilities. This study presents the results from a cross-sectional analysis of pregnant women enrolled in the Hypertension Treatment in Nigeria Program which is aimed at integrating and strengthening hypertension care in primary health care centres.

METHODS: A descriptive analysis of the baseline results from the Hypertension Treatment in Nigeria Program was performed. Baseline blood pressures, treatment and control rates of pregnant women were analysed and …

Altered Signaling And Desensitization Responses In Pth1r Mutants Associated With Eiken Syndrome, Ignacio Portales-Castillo, Thomas Dean, Ross W Cheloha, Brendan A Creemer, Jean-Pierre Vilardaga, Sofya Savransky, Ashok Khatri, Harald Jüppner, Thomas J Gardella

2020-Current year OA Pubs

The parathyroid hormone receptor type 1 (PTH1R) is a G protein-coupled receptor that plays key roles in regulating calcium homeostasis and skeletal development via binding the ligands, PTH and PTH-related protein (PTHrP), respectively. Eiken syndrome is a rare disease of delayed bone mineralization caused by homozygous PTH1R mutations. Of the three mutations identified so far, R485X, truncates the PTH1R C-terminal tail, while E35K and Y134S alter residues in the receptor's amino-terminal extracellular domain. Here, using a variety of cell-based assays, we show that R485X increases the receptor's basal rate of cAMP signaling and decreases its capacity to recruit β-arrestin2 upon …

Combinatorial Bcl2 Family Expression In Acute Myeloid Leukemia Stem Cells Predicts Clinical Response To Azacitidine/Venetoclax, Alexander Waclawiczek, Darja Karpova, Et Al.

2020-Current year OA Pubs

UNLABELLED: The BCL2 inhibitor venetoclax (VEN) in combination with azacitidine (5-AZA) is currently transforming acute myeloid leukemia (AML) therapy. However, there is a lack of clinically relevant biomarkers that predict response to 5-AZA/VEN. Here, we integrated transcriptomic, proteomic, functional, and clinical data to identify predictors of 5-AZA/VEN response. Although cultured monocytic AML cells displayed upfront resistance, monocytic differentiation was not clinically predictive in our patient cohort. We identified leukemic stem cells (LSC) as primary targets of 5-AZA/VEN whose elimination determined the therapy outcome. LSCs of 5-AZA/VEN-refractory patients displayed perturbed apoptotic dependencies. We developed and validated a flow cytometry-based "Mediators of …

Evaluating The Use Of Blood Pressure Polygenic Risk Scores Across Race/Ethnic Background Groups, Nuzulul Kurniansyah, C Charles Gu, Et Al.

2020-Current year OA Pubs

We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare "clumping-and-thresholding" (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs …

Longitudinal Analysis Of Change In Mammographic Density In Each Breast And Its Association With Breast Cancer Risk, Shu Jiang, Debbie L Bennett, Bernard A Rosner, Graham A Colditz

2020-Current year OA Pubs

IMPORTANCE: Although breast density is an established risk factor for breast cancer, longitudinal changes in breast density have not been extensively studied to determine whether this factor is associated with breast cancer risk.

OBJECTIVE: To prospectively evaluate the association between change in mammographic density in each breast over time and risk of subsequent breast cancer.

DESIGN, SETTING, AND PARTICIPANTS: This nested case-control cohort study was sampled from the Joanne Knight Breast Health Cohort of 10 481 women free from cancer at entry and observed from November 3, 2008, to October 31, 2020, with routine screening mammograms every 1 to 2 …

Acinetobacter Baumannii Atcc 17978 Encodes A Microcin System With Antimicrobial Properties For Contact-Independent Competition, Fabiana Bisaro, Howard A Shuman, Mario F Feldman, Michael J Gebhardt, Stefan Pukatzki

2020-Current year OA Pubs

No abstract provided.

Crypticproteindb: An Integrated Database Of Proteome And Immunopeptidome Derived Non-Canonical Cancer Proteins, Ghofran Othoum, Christopher A Maher

2020-Current year OA Pubs

Translated non-canonical proteins derived from noncoding regions or alternative open reading frames (ORFs) can contribute to critical and diverse cellular processes. In the context of cancer, they also represent an under-appreciated source of targets for cancer immunotherapy through their tumor-enriched expression or by harboring somatic mutations that produce neoantigens. Here, we introduce the largest integration and proteogenomic analysis of novel peptides to assess the prevalence of non-canonical ORFs (ncORFs) in more than 900 patient proteomes and 26 immunopeptidome datasets across 14 cancer types. The integrative proteogenomic analysis of whole-cell proteomes and immunopeptidomes revealed peptide support for a nonredundant set of …

Characterization Of Cell-Type Specific Circular Rnas Associated With Colorectal Cancer Metastasis, Sidi Zhao, Amy Ly, Jacqueline L Mudd, Emily B Rozycki, Jace Webster, Emily Coonrod, Ghofran Othoum, Jingqin Luo, Ha X Dang, Ryan C Fields, Christopher A Maher

2020-Current year OA Pubs

Colorectal cancer (CRC) is the most common gastrointestinal malignancy and a leading cause of cancer deaths in the United States. More than half of CRC patients develop metastatic disease (mCRC) with an average 5-year survival rate of 13%. Circular RNAs (circRNAs) have recently emerged as important tumorigenesis regulators; however, their role in mCRC progression remains poorly characterized. Further, little is known about their cell-type specificity to elucidate their functions in the tumor microenvironment (TME). To address this, we performed total RNA sequencing (RNA-seq) on 30 matched normal, primary and metastatic samples from 14 mCRC patients. Additionally, five CRC cell lines …

Interleukin-18 Signaling Promotes Activation Of Hepatic Stellate Cells In Mouse Liver Fibrosis, Jana Knorr, Joel D. Schilling, Et Al.

2020-Current year OA Pubs

BACKGROUND AND AIMS: Nucleotide-binding oligomerization domain-like receptor-family pyrin domain-containing 3 (NLRP3) inflammasome activation has been shown to result in liver fibrosis. Mechanisms and downstream signaling remain incompletely understood. Here, we studied the role of IL-18 in hepatic stellate cells (HSCs), and its impact on liver fibrosis.

APPROACH AND RESULTS: We observed significantly increased serum levels of IL-18 (128.4 pg/ml vs. 74.9 pg/ml) and IL-18 binding protein (BP; 46.50 ng/ml vs. 15.35 ng/ml) in patients with liver cirrhosis compared with healthy controls. Single cell RNA sequencing data showed that an immunoregulatory subset of murine HSCs highly expresses Il18 and Il18r1 . …

Clinical Programs For Cardiometabolic Health For South Asian Patients In The United States: A Review Of Key Program Components, Reeti K Gulati, Mustafa Husaini, Rajesh Dash, Jaideep Patel, Nilay S Shah

2020-Current year OA Pubs

Medical literature shows that South Asians have approximately a 2-fold higher risk of atherosclerotic cardiovascular disease (CVD) compared with other populations. Given this high prevalence, clinical programs to promote cardiovascular health have emerged in the United States that are dedicated to clinical care for South Asian individuals. In this review, we have summarized the key characteristics of clinical programs in the U.S. dedicated to preventing and managing CVD in South Asian American patients. These clinical centers have many unique components in common that are catered to South Asian patient populations including ethnicity concordance of clinical providers, intensive cardiovascular screening protocols …

Rare Dysfunctional Complement Factor I Genetic Variants And Progression To Advanced Age-Related Macular Degeneration, Johanna M Seddon, Bernard Rosner, Dikha De, Tianxiao Huan, Anuja Java, John Atkinson

2020-Current year OA Pubs

PURPOSE: To evaluate associations between rare dysfunctional

DESIGN: Prospective, longitudinal study.

PARTICIPANTS: Patients aged 55 to 80 years at baseline identifying as White with non-AAMD in 1 or both eyes at baseline were included. Follow-up grades were assigned as early, intermediate, or AAMD (GA or NV).

METHODS: Analyses were performed using the Seddon Longitudinal Cohort Study (N = 2116 subjects, 3901 eyes, and mean follow-up of 8.3 years) and the Age-Related Eye Disease Study (N = 2837 subjects, 5200 eyes, and mean follow-up of 9.2 years).

MAIN OUTCOME MEASURES: Progression to AAMD, GA, or NV.

RESULTS: In the prospective cohort …

Assessment And Management Of Older Adults Undergoing Pci, Part 1: A Jacc: Advances Expert Panel, Michael G Nanna, Michael W Rich, Et Al.

2020-Current year OA Pubs

As the population ages, older adults represent an increasing proportion of patients referred to the cardiac catheterization laboratory. Older adults are the highest-risk group for morbidity and mortality, particularly after complex, high-risk percutaneous coronary interventions. Structured risk assessment plays a key role in differentiating patients who are likely to derive net benefit vs those who have disproportionate risks for harm. Conventional risk assessment tools from national cardiovascular societies typically rely on 3 pillars: 1) cardiovascular risk; 2) physiologic and hemodynamic risk; and 3) anatomic and procedural risks. We propose adding a fourth pillar: geriatric syndromes, as geriatric domains can supersede …

Cat Lca-Crx Model, Homozygous For An Antimorphic Mutation Has A Unique Phenotype, Laurence M Occelli, Nicholas M Tran, Shiming Chen, Simon M Petersen-Jones

2020-Current year OA Pubs

PURPOSE: Mutations in the CRX transcription factor are associated with dominant retinopathies often with more severe macular changes. The CRX-mutant cat (Rdy-A182d2) is the only animal model with the equivalent of the critical retinal region for high-acuity vision, the macula. Heterozygous cats (CRXRdy/+) have a severe phenotype modeling Leber congenital amaurosis. This study reports the distinct ocular phenotype of homozygous cats (CRXRdy/Rdy).

METHODS: Gene expression changes were assessed at both mRNA and protein levels. Changes in globe morphology and retinal structure were analyzed.

RESULTS: CRXRdy/Rdy cats had high levels of mutant CRX mRNA and protein. The expression of photoreceptor target …

Tarlatamab, A First-In-Class Dll3-Targeted Bispecific T-Cell Engager, In Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study, Luis Paz-Ares, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

PURPOSE: Small-cell lung cancer (SCLC) is an aggressive malignancy with limited treatments. Delta-like ligand 3 (DLL3) is aberrantly expressed in most SCLC. Tarlatamab (AMG 757), a bispecific T-cell engager molecule, binds both DLL3 and CD3 leading to T-cellb-mediated tumor lysis. Herein, we report phase I results of tarlatamab in patients with SCLC.

PATIENTS AND METHODS: This study evaluated tarlatamab in patients with relapsed/refractory SCLC. The primary end point was safety. Secondary end points included antitumor activity by modified RECIST 1.1, overall survival, and pharmacokinetics.

RESULTS: By July 19, 2022, 107 patients received tarlatamab in dose exploration (0.003 to 100 mg; …

Associations Between Socioeconomic Status, Obesity, Cognition, And White Matter Microstructure In Children, Zhaolong Adrian Li, Yuqi Cai, Rita L Taylor, Sarah A Eisenstein, Deanna M Barch, Scott Marek, Tamara Hershey

2020-Current year OA Pubs

IMPORTANCE: Lower neighborhood and household socioeconomic status (SES) are associated with negative health outcomes and altered brain structure in children. It is unclear whether such findings extend to white matter and via what mechanisms.

OBJECTIVE: To assess whether and how neighborhood and household SES are independently associated with children's white matter microstructure and examine whether obesity and cognitive performance (reflecting environmental cognitive and sensory stimulation) are plausible mediators.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used baseline data from participants in the Adolescent Brain Cognitive Development (ABCD) study. Data were collected at 21 US sites, and school-based recruitment was used …

Temperament & Character Account For Brain Functional Connectivity At Rest: A Diathesis-Stress Model Of Functional Dysregulation In Psychosis, Igor Zwir, Javier Arnedo, Alberto Mesa, Coral Del Val, Gabriel A De Erausquin, C Robert Cloninger

2020-Current year OA Pubs

The human brain's resting-state functional connectivity (rsFC) provides stable trait-like measures of differences in the perceptual, cognitive, emotional, and social functioning of individuals. The rsFC of the prefrontal cortex is hypothesized to mediate a person's rational self-government, as is also measured by personality, so we tested whether its connectivity networks account for vulnerability to psychosis and related personality configurations. Young adults were recruited as outpatients or controls from the same communities around psychiatric clinics. Healthy controls (n = 30) and clinically stable outpatients with bipolar disorder (n = 35) or schizophrenia (n = 27) were diagnosed by structured interviews, and …

Ex Vivo Nonbiomaterial Gel-Based Model For Endoscopic Training, Ameya Deshmukh, Juan Reyes Genere, Ahmad Najdat Bazarbashi

2020-Current year OA Pubs

Video 1Use of artificial model for endoscopic training.

Patients With Stricturing Or Penetrating Crohn's Disease Phenotypes Report High Disease Burden And Treatment Needs, Yanni Fan, Ling Zhang, Negar Omidakhsh, Rhonda L Bohn, Jennifer S Thompson, Kimberly G Brodovicz, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: Crohn's disease (CD) is a chronic autoimmune disease in which inflammation can progress to complications of stricturing and/or penetrating disease. Real-world data on burden of complicated CD phenotypes are limited.

METHODS: We analyzed cross-sectional data from the SPARC IBD (Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease) registry from 2016 to 2020. Four mutually exclusive phenotype cohorts were created: inflammatory CD (CD-I), complicated CD (stricturing CD, penetrating CD, and stricturing and penetrating CD [CD-SP]). Statistical analyses were performed using CD-I as the reference.

RESULTS: A total of 1557 patients were identified: CD-I (n = 674, 43.3%), …

Biological Rhythms In Covid-19 Vaccine Effectiveness In An Observational Cohort Study Of 1.5 Million Patients, Guy Hazan, Or A. Duek, Hillel Alapi, Huram Mok, Alex Ganninger, Elaine Ostendorf, Carrie Gierasch, Gabriel Chodick, David Greenberg, Jeffrey A. Haspel

2020-Current year OA Pubs

BACKGROUNDCircadian rhythms are evident in basic immune processes, but it is unclear if rhythms exist in clinical endpoints like vaccine protection. Here, we examined associations between COVID-19 vaccination timing and effectiveness.METHODSWe retrospectively analyzed a large Israeli cohort with timestamped COVID-19 vaccinations (n = 1,515,754 patients over 12 years old, 99.2% receiving BNT162b2). Endpoints included COVID-19 breakthrough infection and COVID-19-associated emergency department visits and hospitalizations. Our main comparison was among patients vaccinated during morning (800-1159 hours), afternoon (1200-1559 hours), or evening hours (1600-1959 hours). We employed Cox regression to adjust for differences in age, sex, and comorbidities.RESULTSBreakthrough infections differed based on …

American Academy Of Orthopaedic Surgeons Clinical Practice Guideline Summary: Management Of Anterior Cruciate Ligament Injuries, Robert H. Brophy, Kent Jason Lowry

2020-Current year OA Pubs

Management of Anterior Cruciate Ligament Injuries : Evidence-based Clinical Practice Guideline is based on a systematic review of published studies for the treatment of anterior cruciate ligament injurie in both skeletally mature and immature patients. This guideline contains eight recommendations and seven options to assist orthopaedic surgeons and all qualified physicians managing patients with ACL injuries based on the best current available evidence. It is also intended to serve as an information resource for professional healthcare practitioners and developers of practice guidelines and recommendations. In addition to providing pragmatic practice recommendations, this guideline also highlights gaps in the literature and …

Mri Findings Associated With Anterior Cruciate Ligament Tears In National Football League Athletes, Robert H. Brophy, Jon C. Baker, Jana M. Crain, Mackenzie M. Herzog, Ben Stollberg, Edward M. Wojtys, Christina D. Mack

2020-Current year OA Pubs

BACKGROUND: Anterior cruciate ligament (ACL) tears are a high-frequency injury requiring a lengthy recovery in professional American football players. Concomitant pathology associated with ACL tears as identified on magnetic resonance imaging (MRI) is not well understood in these athletes.

PURPOSE: To describe the MRI findings of concomitant injuries associated with ACL tears among athletes in the National Football League (NFL).

STUDY DESIGN: Cross-sectional study; Level of evidence, 3.

METHODS: Of 314 ACL injuries in NFL athletes from 2015 through 2019, 191 complete MRI scans from the time of primary ACL injury were identified and reviewed by 2 fellowship-trained musculoskeletal radiologists. …

Autophagy Prevents Early Proinflammatory Responses And Neutrophil Recruitment During Mycobacterium Tuberculosis Infection Without Affecting Pathogen Burden In Macrophages, Rachel L. Kinsella, Jacqueline M. Kimmey, Asya Smirnov, Reilly Woodson, Margaret R. Gaggioli, Sthefany M. Chavez, Darren Kreamalmeyer, Christina L. Stallings

2020-Current year OA Pubs

The immune response to Mycobacterium tuberculosis infection determines tuberculosis disease outcomes, yet we have an incomplete understanding of what immune factors contribute to a protective immune response. Neutrophilic inflammation has been associated with poor disease prognosis in humans and in animal models during M. tuberculosis infection and, therefore, must be tightly regulated. ATG5 is an essential autophagy protein that is required in innate immune cells to control neutrophil-dominated inflammation and promote survival during M. tuberculosis infection; however, the mechanistic basis for how ATG5 regulates neutrophil recruitment is unknown. To interrogate what innate immune cells require ATG5 to control neutrophil recruitment …

Replicative Acinetobacter Baumannii Strains Interfere With Phagosomal Maturation By Modulating The Vacuolar Ph, Jesus S. Distel, Gisela Di Venanzio, Joseph J. Mackel, David A. Rosen, Mario F. Feldman

2020-Current year OA Pubs

Bacterial pneumonia is a common infection of the lower respiratory tract that can afflict patients of all ages. Multidrug-resistant strains of Acinetobacter baumannii are increasingly responsible for causing nosocomial pneumonias, thus posing an urgent threat. Alveolar macrophages play a critical role in overcoming respiratory infections caused by this pathogen. Recently, we and others have shown that new clinical isolates of A. baumannii, but not the common lab strain ATCC 19606 (19606), can persist and replicate in macrophages within spacious vacuoles that we called Acinetobacter Containing Vacuoles (ACV). In this work, we demonstrate that the modern A. baumannii clinical isolate 398, …

Igg4 Antibodies To The Recombinant Filarial Antigen Wb-Bhp-1 Decrease Dramatically Following Treatment Of Lymphatic Filariasis, Sarah E. Greene, Yuefang Huang, Kurt C. Curtis, Christopher L. King, Peter U. Fischer, Gary J. Weil

2020-Current year OA Pubs

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease and a major cause of chronic disability. Improved diagnostic tests are needed because of long-term persistence of anti-filarial antibodies or circulating filarial antigenemia after treatments that clear microfilaremia. Here, we assess changes in levels of antibodies to the recombinant filarial antigens Wb-Bhp-1, Wb123, and Bm14 after anti-filarial treatment.

METHODOLOGY/PRINCIPAL FINDINGS: IgG4 antibodies to recombinant filarial antigens were assessed by ELISA. We tested serial plasma samples from a clinical trial in Papua New Guinea. Before treatment, 90%, 71% and 99% of participants had antibodies to Wb-Bhp-1, Wb123, and Bm14, respectively. Antibodies to …