165 results on '"Yongchao Ge"'
Search Results
2. Study protocol: Identifying transcriptional regulatory alterations of chronic effects of blast and disturbed sleep in United States Veterans
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Molly J. Sullan, Kelly A. Stearns-Yoder, Zhaoyu Wang, Andrew J. Hoisington, Adam D. Bramoweth, Walter Carr, Yongchao Ge, Hanga Galfalvy, Fatemah Haghighi, and Lisa A. Brenner
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Medicine ,Science - Published
- 2024
3. Association of Blast Exposure in Military Breaching with Intestinal Permeability Blood Biomarkers Associated with Leaky Gut
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Qingkun Liu, Zhaoyu Wang, Shengnan Sun, Jeffrey Nemes, Lisa A. Brenner, Andrew Hoisington, Maciej Skotak, Christina R. LaValle, Yongchao Ge, Walter Carr, and Fatemeh Haghighi
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intestinal permeability ,leaky gut ,blast ,military ,mTBI ,brain–gut axis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Injuries and subclinical effects from exposure to blasts are of significant concern in military operational settings, including tactical training, and are associated with self-reported concussion-like symptomology and physiological changes such as increased intestinal permeability (IP), which was investigated in this study. Time-series gene expression and IP biomarker data were generated from “breachers” exposed to controlled, low-level explosive blast during training. Samples from 30 male participants at pre-, post-, and follow-up blast exposure the next day were assayed via RNA-seq and ELISA. A battery of symptom data was also collected at each of these time points that acutely showed elevated symptom reporting related to headache, concentration, dizziness, and taking longer to think, dissipating ~16 h following blast exposure. Evidence for bacterial translocation into circulation following blast exposure was detected by significant stepwise increase in microbial diversity (measured via alpha-diversity p = 0.049). Alterations in levels of IP protein biomarkers (i.e., Zonulin, LBP, Claudin-3, I-FABP) assessed in a subset of these participants (n = 23) further evidenced blast exposure associates with IP. The observed symptom profile was consistent with mild traumatic brain injury and was further associated with changes in bacterial translocation and intestinal permeability, suggesting that IP may be linked to a decrease in cognitive functioning. These preliminary findings show for the first time within real-world military operational settings that exposures to blast can contribute to IP.
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- 2024
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4. Association of interleukin-6 with suicidal ideation in veterans: a longitudinal perspective
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Shengnan Sun, Caroline M. Wilson, Sharon Alter, Yongchao Ge, Erin A. Hazlett, Marianne Goodman, Rachel Yehuda, Hanga Galfalvy, and Fatemeh Haghighi
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veteran ,suicidal ideation ,suicidal behavior ,depression ,longitudinal ,inflammation ,Psychiatry ,RC435-571 - Abstract
IntroductionStudies showing associations between inflammation in suicide are typically cross-sectional. Present study investigated how cytokine levels track with suicidal ideation and severity longitudinally.MethodsVeterans with a diagnosis of major depressive disorder (MDD) with or without suicide attempt history (MDD/SA n = 38, MDD/NS n = 41) and non-psychiatric non-attempter controls (HC n = 33) were recruited, MDD/SA and HC groups were followed longitudinally at 3 months and 6 months. Blood plasma was collected and processed using Luminex Immunology Multiplex technology.ResultsSignificant differences in depression severity (BDI) and suicidal ideation severity (SSI) were observed across all groups at study entry, wherein MDD/SA group had the highest scores followed by MDD/NS and HC, respectively. Cytokines IL-1β, IL-4, TNF-α, IFN-γ, and IL-6 were examined at study entry and longitudinally, with IL6 levels differing significantly across the groups (p = 0.0123) at study entry. Significant differences in changes in cytokine levels between depressed attempters and the control group were detected for IL-6 (interaction F1,91.77 = 5.58, p = 0.0203) and TNF-α (F1,101.73 = 4.69, p = 0.0327). However, only depressed attempters showed a significant change, in IL-6 and TNF-α levels, decreasing over time [IL-6: b = −0.04, 95% CI = (−0.08, −0.01), p = 0.0245 and TNF-α: b = −0.02, 95% CI = (−0.04, −0.01), p = 0.0196]. Although IL-6 levels were not predictive of suicidal ideation presence [OR = 1.34, 95% CI = (0.77, 2.33), p = 0.3067], IL-6 levels were significantly associated with suicidal ideation severity (b = 0.19, p = 0.0422).DiscussionIL-6 was not associated with presence of suicidal ideation. IL-6 however, was associated with severity of ideation, suggesting that IL-6 may be useful in clinical practice, as an objective marker of heightened suicide risk.
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- 2023
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5. A methylation clock model of mild SARS‐CoV‐2 infection provides insight into immune dysregulation
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Weiguang Mao, Clare M Miller, Venugopalan D Nair, Yongchao Ge, Mary Anne S Amper, Antonio Cappuccio, Mary‐Catherine George, Carl W Goforth, Kristy Guevara, Nada Marjanovic, German Nudelman, Hanna Pincas, Irene Ramos, Rachel S G Sealfon, Alessandra Soares‐Schanoski, Sindhu Vangeti, Mital Vasoya, Dawn L Weir, Elena Zaslavsky, Biobank Team, Seunghee Kim‐Schulze, Sacha Gnjatic, Miriam Merad, Andrew G Letizia, Olga G Troyanskaya, Stuart C Sealfon, and Maria Chikina
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DNA methylation ,machine learning model ,SARS‐CoV‐2 ,temporal dynamics ,trained immunity ,Biology (General) ,QH301-705.5 ,Medicine (General) ,R5-920 - Abstract
Abstract DNA methylation comprises a cumulative record of lifetime exposures superimposed on genetically determined markers. Little is known about methylation dynamics in humans following an acute perturbation, such as infection. We characterized the temporal trajectory of blood epigenetic remodeling in 133 participants in a prospective study of young adults before, during, and after asymptomatic and mildly symptomatic SARS‐CoV‐2 infection. The differential methylation caused by asymptomatic or mildly symptomatic infections was indistinguishable. While differential gene expression largely returned to baseline levels after the virus became undetectable, some differentially methylated sites persisted for months of follow‐up, with a pattern resembling autoimmune or inflammatory disease. We leveraged these responses to construct methylation‐based machine learning models that distinguished samples from pre‐, during‐, and postinfection time periods, and quantitatively predicted the time since infection. The clinical trajectory in the young adults and in a diverse cohort with more severe outcomes was predicted by the similarity of methylation before or early after SARS‐CoV‐2 infection to the model‐defined postinfection state. Unlike the phenomenon of trained immunity, the postacute SARS‐CoV‐2 epigenetic landscape we identify is antiprotective.
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- 2023
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6. Blood RNA alternative splicing events as diagnostic biomarkers for infectious disease
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Zijun Zhang, Natalie Sauerwald, Antonio Cappuccio, Irene Ramos, Venugopalan D. Nair, German Nudelman, Elena Zaslavsky, Yongchao Ge, Angelo Gaitas, Hui Ren, Joel Brockman, Jennifer Geis, Naveen Ramalingam, David King, Micah T. McClain, Christopher W. Woods, Ricardo Henao, Thomas W. Burke, Ephraim L. Tsalik, Carl W. Goforth, Rhonda A. Lizewski, Stephen E. Lizewski, Dawn L. Weir, Andrew G. Letizia, Stuart C. Sealfon, and Olga G. Troyanskaya
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RNA splicing ,diagnostic biomarker ,host response assays ,infectious disease ,SARS-CoV-2 ,viral infection ,Biotechnology ,TP248.13-248.65 ,Biochemistry ,QD415-436 ,Science - Abstract
Summary: Assays detecting blood transcriptome changes are studied for infectious disease diagnosis. Blood-based RNA alternative splicing (AS) events, which have not been well characterized in pathogen infection, have potential normalization and assay platform stability advantages over gene expression for diagnosis. Here, we present a computational framework for developing AS diagnostic biomarkers. Leveraging a large prospective cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and whole-blood RNA sequencing (RNA-seq) data, we identify a major functional AS program switch upon viral infection. Using an independent cohort, we demonstrate the improved accuracy of AS biomarkers for SARS-CoV-2 diagnosis compared with six reported transcriptome signatures. We then optimize a subset of AS-based biomarkers to develop microfluidic PCR diagnostic assays. This assay achieves nearly perfect test accuracy (61/62 = 98.4%) using a naive principal component classifier, significantly more accurate than a gene expression PCR assay in the same cohort. Therefore, our RNA splicing computational framework enables a promising avenue for host-response diagnosis of infection. Motivation: Host-based response assays (HRAs) can often diagnose infectious disease earlier and more precisely than pathogen-based tests. However, the role of RNA alternative splicing (AS) in HRAs remains unexplored, as existing HRAs are restricted to gene expression signatures. We report a computational framework for the identification, optimization, and evaluation of blood AS-based diagnostic assay development for infectious disease. Using SARS-CoV-2 infection as a case study, we demonstrate the improved accuracy of AS biomarkers for COVID-19 diagnosis when compared against six reported transcriptome signatures and when implemented as a microfluidic PCR diagnostic assay.
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- 2023
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7. Serum Fc-Mediated Monocyte Phagocytosis Activity Is Stable for Several Months after SARS-CoV-2 Asymptomatic and Mildly Symptomatic Infection
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Sindhu Vangeti, Sivakumar Periasamy, Peifang Sun, Corey A. Balinsky, Avinash S. Mahajan, Natalia A. Kuzmina, Alessandra Soares-Schanoski, Elizabeth Cooper, Charmagne Beckett, Jan Marayag, Amethyst Marrone, Edgar Nunez, Yongchao Ge, Chad K. Porter, Carl W. Goforth, Stephen E. Lizewski, Rhonda Lizewski, Vihasi Jani, Victor A. Sugiharto, Megan Schilling, Xuechen B. Yu, Nada Marjanovic, Mary Catherine George, Alexander Bukreyev, Stuart C. Sealfon, Andrew G. Letizia, and Irene Ramos
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SARS-CoV-2 ,COVID-19 ,infection ,antibodies ,neutralization ,Fc-mediated functions ,Microbiology ,QR1-502 - Abstract
ABSTRACT We investigated the temporal profile of multiple components of the serological response after asymptomatic or mildly symptomatic SARS-CoV-2 infection, in a cohort of 67 previously SARS-CoV-2 naive young adults, up to 8.5 months after infection. We found a significant decrease of spike IgG and neutralization antibody titers from early (11 to 56 days) to late (4 to 8.5 months) time points postinfection. Over the study period, S1-specific IgG levels declined significantly faster than that of the S2-specific IgG. Further, serum antibodies from PCR-confirmed participants cross-recognized S2, but not S1, of the betacoronaviruses HKU1 and OC43, suggesting a greater degree of cross-reactivity of S2 among betacoronaviruses. Antibody-Dependent Natural Killer cell Activation (ADNKA) was detected at the early time point but significantly decreased at the late time point. Induction of serum Antibody-Dependent Monocyte Phagocytosis (ADMP) was detected in all the infected participants, and its levels remained stable over time. Additionally, a reduced percentage of participants had detectable neutralizing activity against the Beta (50%), Gamma (61 to 67%), and Delta (90 to 94%) variants, both early and late postinfection, compared to the ancestral strain (100%). Antibody binding to S1 and RBD of Beta, Gamma, Delta (1.7 to 2.3-fold decrease), and Omicron (10 to 16-fold decrease) variants was also significantly reduced compared to the ancestral SARS-CoV-2 strain. Overall, we found variable temporal profiles of specific components and functionality of the serological response to SARS-CoV-2 in young adults, which is characterized by lasting, but decreased, neutralizing activity and antibody binding to S1, stable ADMP activity, and relatively stable S2-specific IgG levels. IMPORTANCE Adaptive immunity mediated by antibodies is important for controlling SARS-CoV-2 infection. While vaccines against COVID-19 are currently widely distributed, a high proportion of the global population is still unvaccinated. Therefore, understanding the dynamics and maintenance of the naive humoral immune response to SARS-CoV-2 is of great importance. In addition, long-term responses after asymptomatic infection are not well-characterized, given the challenges in identifying such cases. Here, we investigated the longitudinal humoral profile in a well-characterized cohort of young adults with documented asymptomatic or mildly symptomatic SARS-CoV-2 infection. By analyzing samples collected preinfection, early after infection and during late convalescence, we found that, while neutralizing activity decreased over time, high levels of serum S2 IgG and Antibody-Dependent Monocyte Phagocytosis (ADMP) activity were maintained up to 8.5 months after infection. This suggests that a subset of antibodies with specific functions could contribute to long-term protection against SARS-CoV-2 in convalescent unvaccinated individuals.
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- 2022
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8. Lessons Learned From a Prospective Observational Study of U.S. Marine Recruits During a Supervised Quarantine, Spring‒Fall 2020
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Andrew G. Letizia, MD, Carl W. Goforth, PhD, Yongchao Ge, PhD, Michael S. Termini, MD, Megan A. Schilling, PhD, Victor A. Sugiharto, PhD, Hua Wei Chen, PhD, Irene Ramos, PhD, and Stuart C. Sealfon, MD
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Quarantine ,SARS-CoV-2 screening ,temperature screening ,recruits ,young adults ,SARS-CoV-2 modeling ,Public aspects of medicine ,RA1-1270 - Abstract
Introduction: Quarantining is commonly used to mitigate the spread of SARS-CoV-2. However, questions remain regarding what specific interventions are most effective. Methods: After a 2-week home quarantine, U.S. Marine Corps recruits underwent a supervised 2-week quarantine at a hotel from August 11 to September 21, 2020. All recruits were assessed for symptoms through oral questioning and had their temperatures checked daily. Study participants answered a written clinical questionnaire and were tested for SARS-CoV-2 by polymerase chain reaction shortly after arrival in quarantine and on Days 7 and 14. The results were compared with those of a previously reported Marine-supervised quarantine at a college campus from May until July 2020 utilizing the same study, laboratory, and statistical procedures. Results: A total of 1,401 of 1,514 eligible recruits (92.5%) enrolled in the study, 93.1% of whom were male. At the time of enrollment, 12 of 1,401 (0.9%) participants were polymerase chain reaction positive for SARS-CoV-2, 9 of 1,376 (0.7%) were positive on Day 7, and 1 of 1,358 (0.1%) was positive on Day 14. Only 12 of 22 (54.5%) participants endorsed any symptoms on a study questionnaire, and none of the participants had an elevated temperature or endorsed symptoms during daily screening for SARS-CoV-2. Participation rate (92%) was much greater than the approximately 58.8% (1,848 of 3,143) rate observed in the previous Marine-supervised college campus quarantine, suggesting the changing attitudes of recruits during the pandemic (p
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- 2022
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9. Earlier detection of SARS‐CoV‐2 infection by blood RNA signature microfluidics assay
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Antonio Cappuccio, Jennifer Geis, Yongchao Ge, Venugopalan D. Nair, Naveen Ramalingam, Weiguang Mao, Maria Chikina, Andrew G. Letizia, and Stuart C. Sealfon
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COVID‐19 ,infection diagnosis ,host response assay ,Therapeutics. Pharmacology ,RM1-950 - Published
- 2022
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10. SARS-CoV-2 Seropositivity among US Marine Recruits Attending Basic Training, United States, Spring–Fall 2020
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Andrew G. Letizia, Yongchao Ge, Carl W. Goforth, Dawn L. Weir, Rhonda Lizewski, Stephen Lizewski, Alessandra Soares-Schanoski, Sindhu Vangeti, Nada Marjanovic, Stuart C. Sealfon, and Irene Ramos
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SARS-CoV-2 ,COVID-19 ,seroprevalence ,military recruits ,young adults ,coronavirus disease ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
In a study of US Marine recruits, seroprevalence of severe acute respiratory syndrome coronavirus 2 IgG was 9.0%. Hispanic and non-Hispanic Black participants and participants from states affected earlier in the pandemic had higher seropositivity rates. These results suggest the need for targeted public health strategies among young adults at increased risk for infection.
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- 2021
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11. Asymptomatic SARS-CoV-2 Infection Is Associated With Higher Levels of Serum IL-17C, Matrix Metalloproteinase 10 and Fibroblast Growth Factors Than Mild Symptomatic COVID-19
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Alessandra Soares-Schanoski, Natalie Sauerwald, Carl W. Goforth, Sivakumar Periasamy, Dawn L. Weir, Stephen Lizewski, Rhonda Lizewski, Yongchao Ge, Natalia A. Kuzmina, Venugopalan D. Nair, Sindhu Vangeti, Nada Marjanovic, Antonio Cappuccio, Wan Sze Cheng, Sagie Mofsowitz, Clare M. Miller, Xuechen B. Yu, Mary-Catherine George, Elena Zaslavsky, Alexander Bukreyev, Olga G. Troyanskaya, Stuart C. Sealfon, Andrew G. Letizia, and Irene Ramos
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SARS-CoV-2 ,COVID-19 ,asymptomatic ,serum ,proteomics ,inflammation ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Young adults infected with SARS-CoV-2 are frequently asymptomatic or develop only mild disease. Because capturing representative mild and asymptomatic cases require active surveillance, they are less characterized than moderate or severe cases of COVID-19. However, a better understanding of SARS-CoV-2 asymptomatic infections might shed light into the immune mechanisms associated with the control of symptoms and protection. To this aim, we have determined the temporal dynamics of the humoral immune response, as well as the serum inflammatory profile, of mild and asymptomatic SARS-CoV-2 infections in a cohort of 172 initially seronegative prospectively studied United States Marine recruits, 149 of whom were subsequently found to be SARS-CoV-2 infected. The participants had blood samples taken, symptoms surveyed and PCR tests for SARS-CoV-2 performed periodically for up to 105 days. We found similar dynamics in the profiles of viral load and in the generation of specific antibody responses in asymptomatic and mild symptomatic participants. A proteomic analysis using an inflammatory panel including 92 analytes revealed a pattern of three temporal waves of inflammatory and immunoregulatory mediators, and a return to baseline for most of the inflammatory markers by 35 days post-infection. We found that 23 analytes were significantly higher in those participants that reported symptoms at the time of the first positive SARS-CoV-2 PCR compared with asymptomatic participants, including mostly chemokines and cytokines associated with inflammatory response or immune activation (i.e., TNF-α, TNF-β, CXCL10, IL-8). Notably, we detected 7 analytes (IL-17C, MMP-10, FGF-19, FGF-21, FGF-23, CXCL5 and CCL23) that were higher in asymptomatic participants than in participants with symptoms; these are known to be involved in tissue repair and may be related to the control of symptoms. Overall, we found a serum proteomic signature that differentiates asymptomatic and mild symptomatic infections in young adults, including potential targets for developing new therapies and prognostic tests.
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- 2022
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12. Optimization of the Omni-ATAC protocol to chromatin accessibility profiling in snap-frozen rat adipose and muscle tissues
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Venugopalan D. Nair, Mital Vasoya, Vishnu Nair, Gregory R. Smith, Hanna Pincas, Yongchao Ge, Collin M. Douglas, Karyn A. Esser, and Stuart C. Sealfon
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Ruptor-ATAC ,Science - Abstract
ATAC-seq is a fast and sensitive method for the epigenomic profiling of open chromatin and for mapping of transcription factor binding sites [1]. Despite the development of the Omni-ATAC protocol for the profiling of chromatin accessibility in frozen tissues [2], studies in adipose tissue have been restricted due to technical challenges including the high lipid content of adipocytes and reproducibility issues between replicates. Here, we provide a modified Omni-ATAC protocol that achieves high data reproducibility in various tissue types from rat, including adipose and muscle tissues [3]. • This protocol describes a methodology that enables chromatin accessibility profiling from snap-frozen rat adipose and muscle tissues. • The technique comprises an optimized bead-based tissue homogenization process that substitutes to Dounce homogenization, reduces variability in the experimental procedure, and is adaptable to various tissue types. • In comparison with the Omni-ATAC protocol, the method described here results in improved ATAC-seq data quality that complies with ENCODE quality standards.
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- 2022
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13. Penetrating Ballistic Brain Injury Produces Acute Alterations in Sleep and Circadian-Related Genes in the Rodent Cortex: A Preliminary Study
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Andrea Mountney, Jennifer Blaze, Zhaoyu Wang, Michelle Umali, William Jesse Flerlage, Jacqueline Dougherty, Yongchao Ge, Deborah Shear, and Fatemeh Haghighi
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traumatic brain injury ,circadian ,sleep ,prefrontal cortex ,gene expression ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Traumatic brain injury (TBI) affects millions of Americans each year, with extremely high prevalence in the Veteran community, and sleep disturbance is one of the most commonly reported symptoms. Reduction in the quality and amount of sleep can negatively impact recovery and result in a wide range of behavioral and physiological symptoms, such as impaired cognition, mood and anxiety disorders, and cardiovascular effects. Thus, to improve long-term patient outcomes and develop novel treatments, it is essential to understand the molecular mechanisms involved in sleep disturbance following TBI. In this effort, we performed transcriptional profiling in an established rodent model of penetrating ballistic brain injury (PBBI) in conjunction with continuous sleep/wake EEG/EMG recording of the first 24 h after injury. Rats subjected to PBBI showed profound differences in sleep architecture. Injured animals spent significantly more time in slow wave sleep and less time in REM sleep compared to sham control animals. To identify PBBI-related transcriptional differences, we then performed transcriptome-wide gene expression profiling at 24 h post-injury, which identified a vast array of immune- related genes differentially expressed in the injured cortex as well as sleep-related genes. Further, transcriptional changes associated with total time spent in various sleep stages were identified. Such molecular changes may underlie the pathology and symptoms that emerge following TBI, including neurodegeneration, sleep disturbance, and mood disorders.
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- 2021
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14. Bisulfite Amplicon Sequencing Can Detect Glia and Neuron Cell-Free DNA in Blood Plasma
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Zac Chatterton, Natalia Mendelev, Sean Chen, Walter Carr, Gary H. Kamimori, Yongchao Ge, Andrew J. Dwork, and Fatemeh Haghighi
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cfDNA ,diagnostic ,epigenetic ,neuron ,glia ,neurotrauma ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Sampling the live brain is difficult and dangerous, and withdrawing cerebrospinal fluid is uncomfortable and frightening to the subject, so new sources of real-time analysis are constantly sought. Cell-free DNA (cfDNA) derived from glia and neurons offers the potential for wide-ranging neurological disease diagnosis and monitoring. However, new laboratory and bioinformatic strategies are needed. DNA methylation patterns on individual cfDNA fragments can be used to ascribe their cell-of-origin. Here we describe bisulfite sequencing assays and bioinformatic processing methods to identify cfDNA derived from glia and neurons. In proof-of-concept experiments, we describe the presence of both glia- and neuron-cfDNA in the blood plasma of human subjects following mild trauma. This detection of glia- and neuron-cfDNA represents a significant step forward in the translation of liquid biopsies for neurological diseases.
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- 2021
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15. Antibody Responses to SARS-CoV-2 Following an Outbreak Among Marine Recruits With Asymptomatic or Mild Infection
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Irene Ramos, Carl Goforth, Alessandra Soares-Schanoski, Dawn L. Weir, Emily C. Samuels, Shreshta Phogat, Michelle Meyer, Kai Huang, Colette A. Pietzsch, Yongchao Ge, Brian L. Pike, James Regeimbal, Mark P. Simons, Michael S. Termini, Sindhu Vangeti, Nada Marjanovic, Stephen Lizewski, Rhonda Lizewski, Mary-Catherine George, Venugopalan D. Nair, Gregory R. Smith, Weiguang Mao, Maria Chikina, Christopher C. Broder, Eric D. Laing, Alexander Bukreyev, Stuart C. Sealfon, and Andrew G. Letizia
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SARS-COV-2 ,antibodies ,outbreak ,young adults ,COVID-19 ,Immunologic diseases. Allergy ,RC581-607 - Abstract
We investigated serological responses following a SARS-CoV-2 outbreak in spring 2020 on a US Marine recruit training base. 147 participants that were isolated during an outbreak of respiratory illness were enrolled in this study, with visits approximately 6 and 10 weeks post-outbreak (PO). This cohort is comprised of young healthy adults, ages 18-26, with a high rate of asymptomatic infection or mild symptoms, and therefore differs from previously reported longitudinal studies on humoral responses to SARS-CoV-2, which often focus on more diverse age populations and worse clinical presentation. 80.9% (119/147) of the participants presented with circulating IgG antibodies against SARS-CoV-2 spike (S) receptor-binding domain (RBD) at 6 weeks PO, of whom 97.3% (111/114) remained positive, with significantly decreased levels, at 10 weeks PO. Neutralizing activity was detected in all sera from SARS-CoV-2 IgG positive participants tested (n=38) at 6 and 10 weeks PO, without significant loss between time points. IgG and IgA antibodies against SARS-CoV-2 RBD, S1, S2, and the nucleocapsid (N) protein, as well neutralization activity, were generally comparable between those participants that had asymptomatic infection or mild disease. A multiplex assay including S proteins from SARS-CoV-2 and related zoonotic and human endemic betacoronaviruses revealed a positive correlation for polyclonal cross-reactivity to S after SARS-CoV-2 infection. Overall, young adults that experienced asymptomatic or mild SARS-CoV-2 infection developed comparable humoral responses, with no decrease in neutralizing activity at least up to 10 weeks after infection.
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- 2021
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16. DNA Methylation Patterns of Chronic Explosive Breaching in U.S. Military Warfighters
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Zhaoyu Wang, Caroline M. Wilson, Yongchao Ge, Jeffrey Nemes, Christina LaValle, Angela Boutté, Walter Carr, Gary Kamimori, and Fatemeh Haghighi
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blast exposure ,breacher ,epigenetics ,DNA methylation ,tinnitus ,sleep ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: Injuries from exposure to explosions rose dramatically during the Iraq and Afghanistan wars, which motivated investigation of blast-related neurotrauma. We have undertaken human studies involving military “breachers” —exposed to controlled, low-level blast during a 3-days explosive breaching course.Methods: We screened epigenetic profiles in peripheral blood samples from 59 subjects (in two separate U.S. Military training sessions) using Infinium MethylationEPIC BeadChips. Participants had varying numbers of exposures to blast over their military careers (empirically defined as high ≥ 40, and conversely, low < 39 breaching exposures). Daily self-reported physiological symptoms were recorded. Tinnitus, memory problems, headaches, and sleep disturbances are most frequently reported.Results: We identified 14 significantly differentially methylated regions (DMRs) within genes associated with cumulative blast exposure in participants with high relative to low cumulative blast exposure. Notably, NTSR1 and SPON1 were significantly differentially methylated in high relative to low blast exposed groups, suggesting that sleep dysregulation may be altered in response to chronic cumulative blast exposure. In comparing lifetime blast exposure at baseline (prior to exposure in current training), and top associated symptoms, we identified significant DMRs associated with tinnitus, sleep difficulties, and headache. Notably, we identified KCNN3, SOD3, MUC4, GALR1, and WDR45B, which are implicated in auditory function, as differentially methylated associated with self-reported tinnitus. These findings suggest neurobiological mechanisms behind auditory injuries in our military warfighters and are particularly relevant given tinnitus is not only a primary disability among veterans, but has also been demonstrated in active duty medical records for populations exposed to blast in training. Additionally, we found that differentially methylated regions associated with the genes CCDC68 and COMT track with sleep difficulties, and those within FMOD and TNXB track with pain and headache.Conclusion: Sleep disturbances, as well as tinnitus and chronic pain, are widely reported in U.S. military service members and veterans. As we have previously demonstrated, DNA methylation encapsulates lifetime exposure to blast. The current data support previous findings and recapitulate transcriptional regulatory alterations in genes involved in sleep, auditory function, and pain. These data uncovered novel epigenetic and transcriptional regulatory mechanism underlying the etiological basis of these symptoms.
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- 2020
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17. Blast-Related Mild TBI Alters Anxiety-Like Behavior and Transcriptional Signatures in the Rat Amygdala
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Jennifer Blaze, Inbae Choi, Zhaoyu Wang, Michelle Umali, Natalia Mendelev, Anna E. Tschiffely, Stephen T. Ahlers, Gregory A. Elder, Yongchao Ge, and Fatemeh Haghighi
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mTBI ,amygdala ,blast ,anxiety ,transcriptome ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The short and long-term neurological and psychological consequences of traumatic brain injury (TBI), and especially mild TBI (mTBI) are of immense interest to the Veteran community. mTBI is a common and detrimental result of combat exposure and results in various deleterious outcomes, including mood and anxiety disorders, cognitive deficits, and post-traumatic stress disorder (PTSD). In the current study, we aimed to further define the behavioral and molecular effects of blast-related mTBI using a well-established (3 × 75 kPa, one per day on three consecutive days) repeated blast overpressure (rBOP) model in rats. We exposed adult male rats to the rBOP procedure and conducted behavioral tests for anxiety and fear conditioning at 1–1.5 months (sub-acute) or 12–13 months (chronic) following blast exposure. We also used next-generation sequencing to measure transcriptome-wide gene expression in the amygdala of sham and blast-exposed animals at the sub-acute and chronic time points. Results showed that blast-exposed animals exhibited an anxiety-like phenotype at the sub-acute timepoint but this phenotype was diminished by the chronic time point. Conversely, gene expression analysis at both sub-acute and chronic timepoints demonstrated a large treatment by timepoint interaction such that the most differentially expressed genes were present in the blast-exposed animals at the chronic time point, which also corresponded to a Bdnf-centric gene network. Overall, the current study identified changes in the amygdalar transcriptome and anxiety-related phenotypic outcomes dependent on both blast exposure and aging, which may play a role in the long-term pathological consequences of mTBI.
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- 2020
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18. Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease
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Kaleen M. Lavin, Yongchao Ge, Stuart C. Sealfon, Venugopalan D. Nair, Katarzyna Wilk, Jeremy S. McAdam, Samuel T. Windham, Preeti Lakshman Kumar, Merry-Lynn N. McDonald, and Marcas M. Bamman
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Parkinson’s disease ,high-intensity exercise training ,transcriptome ,neuromuscular ,motor unit ,Physiology ,QP1-981 - Abstract
Parkinson’s disease (PD) is the most common motor neurodegenerative disease, and neuromuscular function deficits associated with PD contribute to disability. Targeting these symptoms, our laboratory has previously evaluated 16-week high-intensity resistance exercise as rehabilitative training (RT) in individuals with PD. We reported significant improvements in muscle mass, neuromuscular function (strength, power, and motor unit activation), indices of neuromuscular junction integrity, total and motor scores on the unified Parkinson’s disease rating scale (UPDRS), and total and sub-scores on the 39-item PD Quality of Life Questionnaire (PDQ-39), supporting the use of RT to reverse symptoms. Our objective was to identify transcriptional networks that may contribute to RT-induced neuromuscular remodeling in PD. We generated transcriptome-wide skeletal muscle RNA-sequencing in 5 participants with PD [4M/1F, 67 ± 2 years, Hoehn and Yahr stages 2 (n = 3) and 3 (n = 2)] before and after 16-week high intensity RT to identify transcriptional networks that may in part underpin RT-induced neuromuscular remodeling in PD. Following RT, 304 genes were significantly upregulated, notably related to remodeling and nervous system/muscle development. Additionally, 402 genes, primarily negative regulators of muscle adaptation, were downregulated. We applied the recently developed Pathway-Level Information ExtractoR (PLIER) method to reveal coordinated gene programs (as latent variables, LVs) that differed in skeletal muscle among young (YA) and old (OA) healthy adults and PD (n = 12 per cohort) at baseline and in PD pre- vs. post-RT. Notably, one LV associated with angiogenesis, axon guidance, and muscle remodeling was significantly lower in PD than YA at baseline and was significantly increased by exercise. A different LV annotated to denervation, autophagy, and apoptosis was increased in both PD and OA relative to YA and was also reduced by 16-week RT in PD. Thus, this analysis identified two novel skeletal muscle transcriptional programs that are dysregulated by PD and aging, respectively. Notably, RT has a normalizing effect on both programs in individuals with PD. These results identify potential molecular transducers of the RT-induced improvements in neuromuscular remodeling and motor function that may aid in optimizing exercise rehabilitation strategies for individuals with PD.
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- 2020
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19. Sedentary and Trained Older Men Have Distinct Circulating Exosomal microRNA Profiles at Baseline and in Response to Acute Exercise
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Venugopalan D. Nair, Yongchao Ge, Side Li, Hanna Pincas, Nimisha Jain, Nitish Seenarine, Mary Anne S. Amper, Bret H. Goodpaster, Martin J. Walsh, Paul M. Coen, and Stuart C. Sealfon
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Acute aerobic exercise ,regular endurance training ,aging ,plasma exosomes ,microRNA profiling ,insulin growth factor-1 signaling ,Physiology ,QP1-981 - Abstract
Exercise has multi-systemic benefits and attenuates the physiological impairments associated with aging. Emerging evidence suggests that circulating exosomes mediate some of the beneficial effects of exercise via the transfer of microRNAs between tissues. However, the impact of regular exercise and acute exercise on circulating exosomal microRNAs (exomiRs) in older populations remains unknown. In the present study, we analyzed circulating exomiR expression in endurance-trained elderly men (n = 5) and age-matched sedentary males (n = 5) at baseline (Pre), immediately after a forty minute bout of aerobic exercise on a cycle ergometer (Post), and three hours after this acute exercise (3hPost). Following the isolation and enrichment of exosomes from plasma, exosome-enriched preparations were characterized and exomiR levels were determined by sequencing. The effect of regular exercise on circulating exomiRs was assessed by comparing the baseline expression levels in the trained and sedentary groups. The effect of acute exercise was determined by comparing baseline and post-training expression levels in each group. Regular exercise resulted in significantly increased baseline expression of three exomiRs (miR-486-5p, miR-215-5p, miR-941) and decreased expression of one exomiR (miR-151b). Acute exercise altered circulating exomiR expression in both groups. However, exomiRs regulated by acute exercise in the trained group (7 miRNAs at Post and 8 at 3hPost) were distinct from those in the sedentary group (9 at Post and 4 at 3hPost). Pathway analysis prediction and reported target validation experiments revealed that the majority of exercise-regulated exomiRs are targeting genes that are related to IGF-1 signaling, a pathway involved in exercise-induced muscle and cardiac hypertrophy. The immediately post-acute exercise exomiR signature in the trained group correlates with activation of IGF-1 signaling, whereas in the sedentary group it is associated with inhibition of IGF-1 signaling. While further validation is needed, including measurements of IGF-1/IGF-1 signaling in blood or skeletal muscle, our results suggest that training status may counteract age-related anabolic resistance by modulating circulating exomiR profiles both at baseline and in response to acute exercise.
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- 2020
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20. Regulatory Architecture of the LβT2 Gonadotrope Cell Underlying the Response to Gonadotropin-Releasing Hormone
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Frederique Ruf-Zamojski, Miguel Fribourg, Yongchao Ge, Venugopalan Nair, Hanna Pincas, Elena Zaslavsky, German Nudelman, Stephanie J. Tuminello, Hideo Watanabe, Judith L. Turgeon, and Stuart C. Sealfon
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LβT2 ,gonadotrope ,gonadotropin-releasing hormone ,chromatin accessibility mapping ,transcription profiling ,single-cell transcriptomics ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
The LβT2 mouse pituitary cell line has many characteristics of a mature gonadotrope and is a widely used model system for studying the developmental processes and the response to gonadotropin-releasing hormone (GnRH). The global epigenetic landscape, which contributes to cell-specific gene regulatory mechanisms, and the single-cell transcriptome response variation of LβT2 cells have not been previously investigated. Here, we integrate the transcriptome and genome-wide chromatin accessibility state of LβT2 cells during GnRH stimulation. In addition, we examine cell-to-cell variability in the transcriptional response to GnRH using Gel bead-in-Emulsion Drop-seq technology. Analysis of a bulk RNA-seq data set obtained 45 min after exposure to either GnRH or vehicle identified 112 transcripts that were regulated >4-fold by GnRH (FDR 4,000 expressed genes/cell, from 1,992 vehicle- and 1,889 GnRH-treated cells. While the individual cell expression patterns showed high cell-to-cell variation, representing both biological and measurement variation, the average expression patterns correlated well with bulk RNA-seq data. Computational assignment of each cell to its precise cell cycle phase showed that the response to GnRH was unaffected by cell cycle. To our knowledge, this study represents the first genome-wide epigenetic and single-cell transcriptomic characterization of this important gonadotrope model. The data have been deposited publicly and should provide a resource for hypothesis generation and further study.
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- 2018
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21. Control of the False Discovery Proportion for Independently Tested Null Hypotheses
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Yongchao Ge and Xiaochun Li
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Probabilities. Mathematical statistics ,QA273-280 - Abstract
Consider the multiple testing problem of testing m null hypotheses H1,…,Hm, among which m0 hypotheses are truly null. Given the P-values for each hypothesis, the question of interest is how to combine the P-values to find out which hypotheses are false nulls and possibly to make a statistical inference on m0. Benjamini and Hochberg proposed a classical procedure that can control the false discovery rate (FDR). The FDR control is a little bit unsatisfactory in that it only concerns the expectation of the false discovery proportion (FDP). The control of the actual random variable FDP has recently drawn much attention. For any level 1−α, this paper proposes a procedure to construct an upper prediction bound (UPB) for the FDP for a fixed rejection region. When 1−α=50%, our procedure is very close to the classical Benjamini and Hochberg procedure. Simultaneous UPBs for all rejection regions' FDPs and the upper confidence bound for the unknown m0 are presented consequently. This new proposed procedure works for finite samples and hence avoids the slow convergence problem of the asymptotic theory.
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- 2012
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22. Evolutionary history of mammalian transposons determined by genome-wide defragmentation.
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Joti Giordano, Yongchao Ge, Yevgeniy Gelfand, György Abrusán, Gary Benson, and Peter E Warburton
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Biology (General) ,QH301-705.5 - Abstract
The constant bombardment of mammalian genomes by transposable elements (TEs) has resulted in TEs comprising at least 45% of the human genome. Because of their great age and abundance, TEs are important in comparative phylogenomics. However, estimates of TE age were previously based on divergence from derived consensus sequences or phylogenetic analysis, which can be unreliable, especially for older more diverged elements. Therefore, a novel genome-wide analysis of TE organization and fragmentation was performed to estimate TE age independently of sequence composition and divergence or the assumption of a constant molecular clock. Analysis of TEs in the human genome revealed approximately 600,000 examples where TEs have transposed into and fragmented other TEs, covering >40% of all TEs or approximately 542 Mbp of genomic sequence. The relative age of these TEs over evolutionary time is implicit in their organization, because newer TEs have necessarily transposed into older TEs that were already present. A matrix of the number of times that each TE has transposed into every other TE was constructed, and a novel objective function was developed that derived the chronological order and relative ages of human TEs spanning >100 million years. This method has been used to infer the relative ages across all four major TE classes, including the oldest, most diverged elements. Analysis of DNA transposons over the history of the human genome has revealed the early activity of some MER2 transposons, and the relatively recent activity of MER1 transposons during primate lineages. The TEs from six additional mammalian genomes were defragmented and analyzed. Pairwise comparison of the independent chronological orders of TEs in these mammalian genomes revealed species phylogeny, the fact that transposons shared between genomes are older than species-specific transposons, and a subset of TEs that were potentially active during periods of speciation.
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- 2007
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23. SARS-CoV-2 Outbreak Dynamics in an Isolated US Military Recruit Training Center With Rigorous Prevention Measures
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Rhonda A. Lizewski, Rachel S. G. Sealfon, Sang Woo Park, Gregory R. Smith, Chad K. Porter, Ana S. Gonzalez-Reiche, Yongchao Ge, Clare M. Miller, Carl W. Goforth, Hanna Pincas, Michael S. Termini, Irene Ramos, Venugopalan D. Nair, Stephen E. Lizewski, Hala Alshammary, Regina Z. Cer, Hua Wei Chen, Mary-Catherine George, Catherine E. Arnold, Lindsay A. Glang, Kyle A. Long, Francisco Malagon, Jan J. Marayag, Edgar Nunez, Gregory K. Rice, Ernesto Santa Ana, Megan A. Schilling, Darci R. Smith, Victor A. Sugiharto, Peifang Sun, Adriana van de Guchte, Zenab Khan, Jayeeta Dutta, Sindhu Vangeti, Logan J. Voegtly, Dawn L. Weir, C. Jessica E. Metcalf, Olga G. Troyanskaya, Kimberly A. Bishop-Lilly, Bryan T. Grenfell, Harm van Bakel, Andrew G. Letizia, and Stuart C. Sealfon
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Male ,Military Personnel ,SARS-CoV-2 ,Epidemiology ,COVID-19 ,Humans ,Female ,Phylogeny ,United States ,Disease Outbreaks - Abstract
Marine recruits training at Parris Island experienced an unexpectedly high rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, despite preventive measures including a supervised, 2-week, pre-entry quarantine. We characterize SARS-CoV-2 transmission in this cohort.Between May and November 2020, we monitored 2,469 unvaccinated, mostly male, Marine recruits prospectively during basic training. If participants tested negative for SARS-CoV-2 by quantitative polymerase chain reaction (qPCR) at the end of quarantine, they were transferred to the training site in segregated companies and underwent biweekly testing for 6 weeks. We assessed the effects of coronavirus disease 2019 (COVID-19) prevention measures on other respiratory infections with passive surveillance data, performed phylogenetic analysis, and modeled transmission dynamics and testing regimens.Preventive measures were associated with drastically lower rates of other respiratory illnesses. However, among the trainees, 1,107 (44.8%) tested SARS-CoV-2-positive, with either mild or no symptoms. Phylogenetic analysis of viral genomes from 580 participants revealed that all cases but one were linked to five independent introductions, each characterized by accumulation of mutations across and within companies, and similar viral isolates in individuals from the same company. Variation in company transmission rates (mean reproduction number R 0 ; 5.5 [95% confidence interval [CI], 5.0, 6.1]) could be accounted for by multiple initial cases within a company and superspreader events. Simulations indicate that frequent rapid-report testing with case isolation may minimize outbreaks.Transmission of wild-type SARS-CoV-2 among Marine recruits was approximately twice that seen in the community. Insights from SARS-CoV-2 outbreak dynamics and mutations spread in a remote, congregate setting may inform effective mitigation strategies.
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- 2022
24. Role of Peripheral Inflammation in Risk of Suicide
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Shengnan Sun, Qingkun Liu, Zhaoyu Wang, Caroline Wilson, Sharon Alter, Yungyu Huang, M. Elizabeth Sublette, Marianne Goodman, Erin Hazlett, Rachel Yehuda, Victoria Arango, Gorazd Rosoklija, Andrew Dwork, Barbara Stanley, Yongchao Ge, Hanga Galfalvy, J. John Mann, and Fatemeh Haghighi
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Biological Psychiatry - Published
- 2023
25. Association between sleep status and lower urinary tract symptoms among men aged 40 or older in Zhengzhou
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Caifang Zheng, Yongchao Ge, Xiaorui Chen, Weihao Shao, Gaili Wang, Bowen Zhang, and Weidong Zhang
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Neuropsychology and Physiological Psychology ,Neurology ,Physiology ,Physiology (medical) - Published
- 2022
26. SARS-CoV-2 seropositivity and subsequent infection risk in healthy young adults: a prospective cohort study
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Daniel Stadlbauer, Hua Wei Chen, Peifang Sun, Ernesto Santa Ana, Russell P. Tracy, Stuart C. Sealfon, Sagie Mofsowitz, Dawn L. Weir, Megan A. Schilling, Venugopalan D. Nair, Florian Krammer, Jan Marayag, William D. Graham, Yongchao Ge, Rhonda A. Lizewski, Daniel Ewing, Edgar Nunez, Mary Catherine George, Alexander Bukreyev, Andrew G. Letizia, Preeti Bharaj, Natalia Kuzmina, Nada Marjanovic, Chad K. Porter, Franca R. Jones, Sindhu Vangeti, Alessandra Soares-Schanoski, Clare M. Miller, Irene Ramos, Michael Termini, Carl Goforth, Corey A. Balinsky, Danielle M. Parent, Stephen E. Lizewski, and Victor A. Sugiharto
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Rate ratio ,law.invention ,Serology ,03 medical and health sciences ,0302 clinical medicine ,law ,Internal medicine ,Quarantine ,medicine ,Humans ,Medical history ,030212 general & internal medicine ,Young adult ,Prospective cohort study ,SARS-CoV-2 ,business.industry ,COVID-19 ,Articles ,Virus Shedding ,030228 respiratory system ,Reinfection ,business ,Risk assessment ,Cohort study - Abstract
Background Whether young adults who are infected with SARS-CoV-2 are at risk of subsequent infection is uncertain. We investigated the risk of subsequent SARS-CoV-2 infection among young adults seropositive for a previous infection. Methods This analysis was performed as part of the prospective COVID-19 Health Action Response for Marines study (CHARM). CHARM included predominantly male US Marine recruits, aged 18–20 years, following a 2-week unsupervised quarantine at home. After the home quarantine period, upon arrival at a Marine-supervised 2-week quarantine facility (college campus or hotel), participants were enrolled and were assessed for baseline SARS-CoV-2 IgG seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein ELISA. Participants also completed a questionnaire consisting of demographic information, risk factors, reporting of 14 specific COVID-19-related symptoms or any other unspecified symptom, and brief medical history. SARS-CoV-2 infection was assessed by PCR at weeks 0, 1, and 2 of quarantine and participants completed a follow-up questionnaire, which included questions about the same COVID-19-related symptoms since the last study visit. Participants were excluded at this stage if they had a positive PCR test during quarantine. Participants who had three negative swab PCR results during quarantine and a baseline serum serology test at the beginning of the supervised quarantine that identified them as seronegative or seropositive for SARS-CoV-2 then went on to basic training at Marine Corps Recruit Depot—Parris Island. Three PCR tests were done at weeks 2, 4, and 6 in both seropositive and seronegative groups, along with the follow-up symptom questionnaire and baseline neutralising antibody titres on all subsequently infected seropositive and selected seropositive uninfected participants (prospective study period). Findings Between May 11, 2020, and Nov 2, 2020, we enrolled 3249 participants, of whom 3168 (98%) continued into the 2-week quarantine period. 3076 (95%) participants, 2825 (92%) of whom were men, were then followed up during the prospective study period after quarantine for 6 weeks. Among 189 seropositive participants, 19 (10%) had at least one positive PCR test for SARS-CoV-2 during the 6-week follow-up (1·1 cases per person-year). In contrast, 1079 (48%) of 2247 seronegative participants tested positive (6·2 cases per person-year). The incidence rate ratio was 0·18 (95% CI 0·11–0·28; p
- Published
- 2021
27. The association of childhood trauma with sleep disturbances and risk of suicide in US veterans
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Amanda Vitale, Sharon Alter, Hanga Galfalvy, Marianne Goodman, Zhaoyu Wang, Rachel E. Harris, Caroline Wilson, Shengnan Sun, Yongchao Ge, Rachel Yehuda, Fatemeh Haghighi, and Erin A. Hazlett
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Hostility ,Impulsivity ,Suicidal Ideation ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,medicine ,Humans ,Risk factor ,Suicidal ideation ,Biological Psychiatry ,Veterans ,Depressive Disorder, Major ,Sleep disorder ,Suicide attempt ,business.industry ,medicine.disease ,030227 psychiatry ,Psychiatry and Mental health ,Cross-Sectional Studies ,Major depressive disorder ,medicine.symptom ,Sleep ,business ,030217 neurology & neurosurgery ,Clinical psychology ,Psychopathology - Abstract
Background Sleep dysregulation is prevalent among veterans and is associated with increased risk of suicidal ideation and behaviors. A confluence of risk factors have been identified to date that contribute to increase risk for suicidal behavior. How these risk factors including childhood trauma, comorbid psychopathology, impulsivity, and hostility together with sleep disturbance contribute to suicide risk remains an open question. These factors have never been examined simultaneously in a unified mediation model, as investigated in the present study, to determine their relative contribution to suicide risk. Methods Veterans (N = 105) were recruited across 3-groups, including Major Depressive Disorder (MDD) with/without a history of a suicide attempt (n = 35 and n = 37, respectively), and non-psychiatric controls, who had no history of mental illness or suicidal behavior (n = 33). The participants were assessed using validated self-report assessments with in-depth phenotyping for relevant risk factors associated with suicidal behavior including childhood adversity, depression severity, impulsivity, hostility, and sleep quality. These factors were included in mediation models using path analysis. Results Across all subjects including those with MDD and non-psychiatric controls, mediation analysis showed that higher levels of childhood trauma had an indirect effect on poor sleep quality (p = 0.001). This effect was orthogonal, being independently mediated by both MDD psychopathology (p = 0.003), and higher traits of impulsivity (p = 0.001) and hostility (p = 0.015). Amongst MDD veterans, childhood trauma was directly associated with increased suicide risk (p = 0.034), irrespective of their severity of depression, or their degree of hostility and impulsivity. Limitations include use of self-report data, and the inability to establish causal inferences with cross-sectional design. Conclusion Childhood adversity as a significant pre-deployment risk factor for disturbed sleep and elevated suicide risk, potentially important for incorporation in clinical practice for suicide.
- Published
- 2021
28. Pre-infection antiviral innate immunity contributes to sex differences in SARS-CoV-2 infection
- Author
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Natalie Sauerwald, Zijun Zhang, Irene Ramos, Venugopalan D. Nair, Alessandra Soares-Schanoski, Yongchao Ge, Weiguang Mao, Hala Alshammary, Ana S. Gonzalez-Reiche, Adriana van de Guchte, Carl W. Goforth, Rhonda A. Lizewski, Stephen E. Lizewski, Mary Anne S. Amper, Mital Vasoya, Nitish Seenarine, Kristy Guevara, Nada Marjanovic, Clare M. Miller, German Nudelman, Megan A. Schilling, Rachel S.G. Sealfon, Michael S. Termini, Sindhu Vangeti, Dawn L. Weir, Elena Zaslavsky, Maria Chikina, Ying Nian Wu, Harm Van Bakel, Andrew G. Letizia, Stuart C. Sealfon, and Olga G. Troyanskaya
- Subjects
Male ,Proteomics ,Young Adult ,Sex Characteristics ,Histology ,SARS-CoV-2 ,Humans ,COVID-19 ,Female ,Cell Biology ,Interferons ,Immunity, Innate ,Pathology and Forensic Medicine - Abstract
Male sex is a major risk factor for SARS-CoV-2 infection severity. To understand the basis for this sex difference, we studied SARS-CoV-2 infection in a young adult cohort of United States Marine recruits. Among 2,641 male and 244 female unvaccinated and seronegative recruits studied longitudinally, SARS-CoV-2 infections occurred in 1,033 males and 137 females. We identified sex differences in symptoms, viral load, blood transcriptome, RNA splicing, and proteomic signatures. Females had higher pre-infection expression of antiviral interferon-stimulated gene (ISG) programs. Causal mediation analysis implicated ISG differences in number of symptoms, levels of ISGs, and differential splicing of CD45 lymphocyte phosphatase during infection. Our results indicate that the antiviral innate immunity set point causally contributes to sex differences in response to SARS-CoV-2 infection. A record of this paper's transparent peer review process is included in the supplemental information.
- Published
- 2022
29. flowPeaks: a fast unsupervised clustering for flow cytometry data via K-means and density peak finding.
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Yongchao Ge and Stuart C. Sealfon
- Published
- 2012
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30. MethylomeDB: a database of DNA methylation profiles of the brain.
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Yurong Xin, Benjamin Chanrion, Anne H. O'Donnell, Maria Milekic, Ramiro Costa, Yongchao Ge, and Fatemeh G. Haghighi
- Published
- 2012
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31. Acute and Chronic Molecular Signatures and Associated Symptoms of Blast Exposure in Military Breachers
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Hanga Galfalvy, Walter Carr, Zhaoyu Wang, Gregory A. Elder, Yongchao Ge, Fatemeh Haghighi, Stephen T. Ahlers, Matthew L LoPresti, Natalia Mendelev, Gary H. Kamimori, Caroline Wilson, and Angela M. Yarnell
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Adult ,Male ,030506 rehabilitation ,Chemokine ,Time Factors ,Transcription, Genetic ,Explosions ,blast overpressure ,03 medical and health sciences ,0302 clinical medicine ,Blast Injuries ,Gene expression ,Medicine ,Humans ,Epigenetics ,sleep ,tinnitus ,Gene ,biology ,epigenetics ,business.industry ,Sequence Analysis, RNA ,traumatic brain injury ,Methylation ,Original Articles ,DNA Methylation ,Fold change ,Differentially methylated regions ,Military Personnel ,Immunology ,DNA methylation ,biology.protein ,Cytokines ,Neurology (clinical) ,Inflammation Mediators ,0305 other medical science ,business ,030217 neurology & neurosurgery ,Biomarkers - Abstract
Injuries from exposure to explosions rose dramatically during the Iraq and Afghanistan wars, which motivated investigations of blast-related neurotrauma and operational breaching. In this study, military “breachers” were exposed to controlled, low-level blast during a 10-day explosive breaching course. Using an omics approach, we assessed epigenetic, transcriptional, and inflammatory profile changes in blood from operational breaching trainees, with varying levels of lifetime blast exposure, along with daily self-reported symptoms (with tinnitus, headaches, and sleep disturbances as the most frequently reported). Although acute exposure to blast did not confer epigenetic changes, specifically in DNA methylation, differentially methylated regions (DMRs) with coordinated gene expression changes associated with chronic lifetime cumulative blast exposures were identified. The accumulative effect of blast showed increased methylation of PAX8 antisense transcript with coordinated repression of gene expression, which has been associated with sleep disturbance. DNA methylation analyses conducted in conjunction with reported symptoms of tinnitus in the low vs. high blast incidents groups identified DMRS in KCNE1 and CYP2E1 genes. KCNE1 and CYP2E1 showed the expected inverse correlation between DNA methylation and gene expression, which have been previously implicated in noise related hearing loss. Although no significant transcriptional changes were observed in samples obtained at the onset of the training course relative to chronic cumulative blast, we identified a large number of transcriptional perturbations acutely pre- versus post-blast exposure. Acutely, 67 robustly differentially expressed genes (fold change ≥1.5), including UFC1 and YOD1, ubiquitin-related proteins were identified. Inflammatory analyses of cytokines and chemokines revealed dysregulation of MCP-1, GCSF, HGF, MCSF, and RANTES acutely following blast exposure. These data show the importance of an omics approach, revealing that transcriptional and inflammatory biomarkers capture acute low-level blast overpressure exposure, whereas DNA methylation marks encapsulate chronic long-term symptoms.
- Published
- 2020
32. Transcription factor GATA2 may potentiate follicle-stimulating hormone production in mice via induction of the BMP antagonist gremlin in gonadotrope cells
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Gauthier Schang, Luisina Ongaro, Emilie Brûlé, Xiang Zhou, Ying Wang, Ulrich Boehm, Frederique Ruf-Zamojski, Michel Zamojski, Natalia Mendelev, Nitish Seenarine, Mary Anne Amper, Venugopalan Nair, Yongchao Ge, Stuart C. Sealfon, and Daniel J. Bernard
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Male ,Cell Biology ,Gonadotrophs ,Biochemistry ,Activins ,GATA2 Transcription Factor ,Mice ,Bone Morphogenetic Proteins ,Follicle Stimulating Hormone, beta Subunit ,Animals ,Intercellular Signaling Peptides and Proteins ,Female ,Follicle Stimulating Hormone ,Molecular Biology - Abstract
Mammalian reproduction depends on the gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone, which are secreted by pituitary gonadotrope cells. The zinc-finger transcription factor GATA2 was previously implicated in FSH production in male mice; however, its mechanisms of action and role in females were not determined. To directly address GATA2 function in gonadotropes, we generated and analyzed gonadotrope-specific Gata2 KO mice using the Cre-lox system. We found that while conditional KO (cKO) males exhibited ∼50% reductions in serum FSH levels and pituitary FSHβ subunit (Fshb) expression relative to controls, FSH production was apparently normal in cKO females. In addition, RNA-seq analysis of purified gonadotropes from control and cKO males revealed a profound decrease in expression of gremlin (Grem1), a bone morphogenetic protein (BMP) antagonist. We show Grem1 was expressed in gonadotropes, but not other cell lineages, in the adult male mouse pituitary. Furthermore, Gata2, Grem1, and Fshb mRNA levels were significantly higher in the pituitaries of WT males relative to females but decreased in males treated with estradiol and increased following ovariectomy in control but not cKO females. Finally, we found that recombinant gremlin stimulated Fshb expression in pituitary cultures from WT mice. Collectively, the data suggest that GATA2 promotes Grem1 expression in gonadotropes and that the gremlin protein potentiates FSH production. The mechanisms of gremlin action have not yet been established but may involve attenuation of BMP binding to activin type II receptors in gonadotropes, facilitating induction of Fshb transcription by activins or related ligands.
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- 2022
33. Asymptomatic SARS-CoV-2 Infection Is Associated With Higher Levels of Serum IL-17C, Matrix Metalloproteinase 10 and Fibroblast Growth Factors Than Mild Symptomatic COVID-19
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Alessandra Soares-Schanoski, Natalie Sauerwald, Carl W. Goforth, Sivakumar Periasamy, Dawn L. Weir, Stephen Lizewski, Rhonda Lizewski, Yongchao Ge, Natalia A. Kuzmina, Venugopalan D. Nair, Sindhu Vangeti, Nada Marjanovic, Antonio Cappuccio, Wan Sze Cheng, Sagie Mofsowitz, Clare M. Miller, Xuechen B. Yu, Mary-Catherine George, Elena Zaslavsky, Alexander Bukreyev, Olga G. Troyanskaya, Stuart C. Sealfon, Andrew G. Letizia, and Irene Ramos
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Fibroblast Growth Factors ,Proteomics ,Matrix Metalloproteinase 10 ,SARS-CoV-2 ,Immunology ,Interleukin-17 ,Immunology and Allergy ,COVID-19 ,Humans - Abstract
Young adults infected with SARS-CoV-2 are frequently asymptomatic or develop only mild disease. Because capturing representative mild and asymptomatic cases require active surveillance, they are less characterized than moderate or severe cases of COVID-19. However, a better understanding of SARS-CoV-2 asymptomatic infections might shed light into the immune mechanisms associated with the control of symptoms and protection. To this aim, we have determined the temporal dynamics of the humoral immune response, as well as the serum inflammatory profile, of mild and asymptomatic SARS-CoV-2 infections in a cohort of 172 initially seronegative prospectively studied United States Marine recruits, 149 of whom were subsequently found to be SARS-CoV-2 infected. The participants had blood samples taken, symptoms surveyed and PCR tests for SARS-CoV-2 performed periodically for up to 105 days. We found similar dynamics in the profiles of viral load and in the generation of specific antibody responses in asymptomatic and mild symptomatic participants. A proteomic analysis using an inflammatory panel including 92 analytes revealed a pattern of three temporal waves of inflammatory and immunoregulatory mediators, and a return to baseline for most of the inflammatory markers by 35 days post-infection. We found that 23 analytes were significantly higher in those participants that reported symptoms at the time of the first positive SARS-CoV-2 PCR compared with asymptomatic participants, including mostly chemokines and cytokines associated with inflammatory response or immune activation (i.e., TNF-α, TNF-β, CXCL10, IL-8). Notably, we detected 7 analytes (IL-17C, MMP-10, FGF-19, FGF-21, FGF-23, CXCL5 and CCL23) that were higher in asymptomatic participants than in participants with symptoms; these are known to be involved in tissue repair and may be related to the control of symptoms. Overall, we found a serum proteomic signature that differentiates asymptomatic and mild symptomatic infections in young adults, including potential targets for developing new therapies and prognostic tests.
- Published
- 2021
34. Divergent Synthesis of Contorted Polycyclic Aromatics Containing Pentagons, Heptagon, and/or Azulene
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Qinghai Zhou, Wenhua Li, Chaoran Qi, Yuying Lan, Taifeng Liu, Lanting Xu, Lei Yang, Yangyang Pan, Yongchao Ge, Shengxiong Xiao, Hexing Li, Yang-Kun Qu, Junxia Ren, and Wenying Dai
- Subjects
chemistry.chemical_compound ,Chemistry ,Computational chemistry ,Organic Chemistry ,Molecule ,Heptagon ,Physical and Theoretical Chemistry ,Azulene ,Biochemistry ,Divergent synthesis - Abstract
Divergent synthesis of four contorted aromatics containing pentagons, a heptagon, and/or an azulene from the same difluorenyl pentacenediene precursor were realized in one step. The subtle differences in molecular structure were confirmed by X-ray crystallography. The mechanisms for the control of different products, which involve a ring-expansion rearrangement, Scholl reactions, and/or Mallory cyclization were proposed on the basis of control experiments and DFT calculations. Such development adds good structure versatility and materials accessibility to the study of contorted aromatics.
- Published
- 2021
35. P692. Systemic Inflammation Positively Correlates With High Suicide Ideation in Clood and CNS
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Fatemeh Haghighi, Qingkun Liu, Shengnan Sun, Zhaoyu Wang, Yongchao Ge, Yung-yu Huang, M. Elizabeth Sublette, Victoria Arango, Gorazd Rosoklija, Andrew J. Dwork, Barbara Stanley, Hanga Galfalvy, and J. John Mann
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Biological Psychiatry - Published
- 2022
36. Optimization of the Omni-ATAC protocol to chromatin accessibility profiling in snap-frozen rat adipose and muscle tissues
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Venugopalan D. Nair, Mital Vasoya, Vishnu Nair, Gregory R. Smith, Hanna Pincas, Yongchao Ge, Collin M. Douglas, Karyn A. Esser, and Stuart C. Sealfon
- Subjects
Medical Laboratory Technology ,Clinical Biochemistry - Abstract
ATAC-seq is a fast and sensitive method for the epigenomic profiling of open chromatin and for mapping of transcription factor binding sites [1]. Despite the development of the Omni-ATAC protocol for the profiling of chromatin accessibility in frozen tissues [2], studies in adipose tissue have been restricted due to technical challenges including the high lipid content of adipocytes and reproducibility issues between replicates. Here, we provide a modified Omni-ATAC protocol that achieves high data reproducibility in various tissue types from rat, including adipose and muscle tissues [3].•This protocol describes a methodology that enables chromatin accessibility profiling from snap-frozen rat adipose and muscle tissues.•The technique comprises an optimized bead-based tissue homogenization process that substitutes to Dounce homogenization, reduces variability in the experimental procedure, and is adaptable to various tissue types.•In comparison with the Omni-ATAC protocol, the method described here results in improved ATAC-seq data quality that complies with ENCODE quality standards.
- Published
- 2021
37. Viable virus shedding during SARS-CoV-2 reinfection
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Darci R. Smith, Ernesto Santa Ana, Clare M. Miller, Andrew G. Letizia, Rachel Sealfon, Olga G. Troyanskaya, Harm van Bakel, Rhonda A. Lizewski, Michael Termini, Yongchao Ge, Mary Catherine George, Edgar Nunez, Stephen E. Lizewski, Chad K. Porter, Adriana van de Guchte, Dawn L. Weir, Jan Marayag, Ana S. Gonzalez-Reiche, Hua Wei Chen, Irene Ramos, Hala Alshammary, Victor A. Sugiharto, Peifang Sun, Alessandra Soares-Schanoski, Carl Goforth, Megan A. Schilling, Sindhu Vangeti, and Stuart C. Sealfon
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Pulmonary and Respiratory Medicine ,Male ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Adolescent ,business.industry ,SARS-CoV-2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,COVID-19 ,Antibodies, Viral ,Virology ,Risk Assessment ,COVID-19 Serological Testing ,Cohort Studies ,Young Adult ,Correspondence ,Quarantine ,Medicine ,Humans ,Female ,Prospective Studies ,Viral shedding ,business - Abstract
Whether young adults who are infected with SARS-CoV-2 are at risk of subsequent infection is uncertain. We investigated the risk of subsequent SARS-CoV-2 infection among young adults seropositive for a previous infection.This analysis was performed as part of the prospective COVID-19 Health Action Response for Marines study (CHARM). CHARM included predominantly male US Marine recruits, aged 18-20 years, following a 2-week unsupervised quarantine at home. After the home quarantine period, upon arrival at a Marine-supervised 2-week quarantine facility (college campus or hotel), participants were enrolled and were assessed for baseline SARS-CoV-2 IgG seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein ELISA. Participants also completed a questionnaire consisting of demographic information, risk factors, reporting of 14 specific COVID-19-related symptoms or any other unspecified symptom, and brief medical history. SARS-CoV-2 infection was assessed by PCR at weeks 0, 1, and 2 of quarantine and participants completed a follow-up questionnaire, which included questions about the same COVID-19-related symptoms since the last study visit. Participants were excluded at this stage if they had a positive PCR test during quarantine. Participants who had three negative swab PCR results during quarantine and a baseline serum serology test at the beginning of the supervised quarantine that identified them as seronegative or seropositive for SARS-CoV-2 then went on to basic training at Marine Corps Recruit Depot-Parris Island. Three PCR tests were done at weeks 2, 4, and 6 in both seropositive and seronegative groups, along with the follow-up symptom questionnaire and baseline neutralising antibody titres on all subsequently infected seropositive and selected seropositive uninfected participants (prospective study period).Between May 11, 2020, and Nov 2, 2020, we enrolled 3249 participants, of whom 3168 (98%) continued into the 2-week quarantine period. 3076 (95%) participants, 2825 (92%) of whom were men, were then followed up during the prospective study period after quarantine for 6 weeks. Among 189 seropositive participants, 19 (10%) had at least one positive PCR test for SARS-CoV-2 during the 6-week follow-up (1·1 cases per person-year). In contrast, 1079 (48%) of 2247 seronegative participants tested positive (6·2 cases per person-year). The incidence rate ratio was 0·18 (95% CI 0·11-0·28; p0·001). Among seropositive recruits, infection was more likely with lower baseline full-length spike protein IgG titres than in those with higher baseline full-length spike protein IgG titres (hazard ratio 0·45 [95% CI 0·32-0·65]; p0·001). Infected seropositive participants had viral loads that were about 10-times lower than those of infected seronegative participants (ORF1ab gene cycle threshold difference 3·95 [95% CI 1·23-6·67]; p=0·004). Among seropositive participants, baseline neutralising titres were detected in 45 (83%) of 54 uninfected and in six (32%) of 19 infected participants during the 6 weeks of observation (ID50 difference p0·0001).Seropositive young adults had about one-fifth the risk of subsequent infection compared with seronegative individuals. Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralisation activity or immunity against subsequent infection. These findings might be relevant for optimisation of mass vaccination strategies.Defense Health Agency and Defense Advanced Research Projects Agency.
- Published
- 2021
38. Cytogenetic, Genomic, and Functional Characterization of Pituitary Gonadotrope Cell Lines
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Cristina Montagna, Jidong Shan, Pranav Nair, Yinghui Song, Stuart C. Sealfon, Hanna Pincas, Pamela L. Mellon, Kevin Kelley, Yongchao Ge, Nika Hines, Judith L Turgeon, Frederique Ruf-Zamojski, Venugopalan D. Nair, Chirine Toufaily, and Daniel J. Bernard
- Subjects
0301 basic medicine ,Cell type ,medicine.drug_class ,gonadotrope cell lines ,Endocrinology, Diabetes and Metabolism ,Cell ,030209 endocrinology & metabolism ,Biology ,FSHB ,LβT2 ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,Copy-number variation ,Research Articles ,L beta T2 ,Human Genome ,STR profiling ,Chromosome ,Karyotype ,Pituitary and Neuroendocrinology ,karyotyping ,Molecular biology ,030104 developmental biology ,medicine.anatomical_structure ,Cell culture ,transcriptional response to GnRH ,SC DNA sequencing ,Gonadotropin ,Biotechnology - Abstract
LβT2 and αT3-1 are important, widely studied cell line models for the pituitary gonadotropes that were generated by targeted tumorigenesis in transgenic mice. LβT2 cells are more mature gonadotrope precursors than αT3-1 cells. Microsatellite authentication patterns, chromosomal characteristics, and their intercellular variation have not been reported. We performed microsatellite and cytogenetic analysis of both cell types at early passage numbers. Short tandem repeat (STR) profiling was consistent with a mixed C57BL/6J × BALB/cJ genetic background, with distinct patterns for each cell type. Spectral karyotyping in αT3-1 cells revealed cell-to-cell variation in chromosome composition and pseudodiploidy. In LβT2 cells, chromosome counting and karyotyping demonstrated pseudotriploidy and high chromosomal variation among cells. Chromosome copy number variation was confirmed by single-cell DNA sequencing. Chromosomal compositions were consistent with a male sex for αT3-1 and a female sex for LβT2 cells. Among LβT2 stocks used in multiple laboratories, we detected two genetically similar but distinguishable lines via STR authentication, LβT2a and LβT2b. The two lines differed in morphological appearance, with LβT2a having significantly smaller cell and nucleus areas. Analysis of immediate early gene and gonadotropin subunit gene expression revealed variations in basal expression and responses to continuous and pulsatile GnRH stimulation. LβT2a showed higher basal levels of Egr1, Fos, and Lhb but lower Fos induction. Fshb induction reached significance only in LβT2b cells. Our study highlights the heterogeneity in gonadotrope cell line genomes and provides reference STR authentication patterns that can be monitored to improve experimental reproducibility and facilitate comparisons of results within and across laboratories.
- Published
- 2019
39. Brain Imaging‐Guided Analysis Reveals DNA Methylation Profiles Correlated with Insular Surface Area and Alcohol Use Disorder
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Yihong Zhao, Zhi-Liang Zheng, and Yongchao Ge
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Adult ,Male ,False discovery rate ,030508 substance abuse ,Medicine (miscellaneous) ,Neuroimaging ,Alcohol use disorder ,Biology ,Toxicology ,Insular cortex ,Article ,Epigenome ,03 medical and health sciences ,0302 clinical medicine ,mental disorders ,medicine ,Humans ,Protein Interaction Maps ,Epigenetics ,Gene ,Cerebral Cortex ,Genetics ,Computational Biology ,Methylation ,DNA Methylation ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,Case-Control Studies ,DNA methylation ,Female ,0305 other medical science ,Alcohol-Related Disorders ,030217 neurology & neurosurgery - Abstract
BACKGROUND Alcohol use disorder (AUD) is a wide-spread, heritable brain disease, but few studies have linked genetic variants or epigenetic factors to brain structures related to AUD in humans, due to many factors including the high-dimensional nature of imaging and genomic data. METHODS To provide potential insights into the links among epigenetic regulation, brain structure, and AUD, we have performed an integrative analysis of brain structural imaging and blood DNA methylome data from 52 AUD and 58 healthy control (HC) subjects collected in the Nathan Kline Institute-Rockland Sample. RESULTS We first found that AUD subjects had significantly larger insular surface area than HC in both left and right hemispheres. We then found that 7,827 DNA methylation probes on the HumanMethylation450K BeadChip had significant correlations with the right insular surface area (false discovery rate [FDR]
- Published
- 2019
40. Prevalence and heritability of benign prostatic hyperplasia and LUTS in men aged 40 years or older in Zhengzhou rural areas
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Quanliang Hou, Yongchao Ge, Weidong Zhang, Tao Wang, Binghui Du, Limin Yue, Bingnan Ren, Huizi Tian, Chengda Zhang, Mengying Ge, and Wenhua Wang
- Subjects
Adult ,Male ,Rural Population ,0301 basic medicine ,China ,medicine.medical_specialty ,Urology ,Prostatic Hyperplasia ,Prostatitis ,urologic and male genital diseases ,03 medical and health sciences ,0302 clinical medicine ,Lower Urinary Tract Symptoms ,Prostate ,Diabetes mellitus ,Internal medicine ,Prevalence ,medicine ,Humans ,Nocturia ,Aged ,Aged, 80 and over ,business.industry ,Age Factors ,Middle Aged ,Heritability ,Hyperplasia ,medicine.disease ,Obesity ,Cross-Sectional Studies ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Case-Control Studies ,030220 oncology & carcinogenesis ,International Prostate Symptom Score ,medicine.symptom ,business - Abstract
Background Benign prostate hyperplasia (BPH) is the most common disease among aging males, but no reports have addressed the prevalence of BPH in Zhengzhou. Therefore, we aimed to understand the prevalence of BPH in men aged 40 years or older in Zhengzhou's rural areas through a cross-sectional study and analyzed the correlation with epidemiologic factors and the heritability of the disease. Materials and methods A multistage sampling method was used to randomly select male respondents in Zhengzhou's rural areas. Men who were 40 years of age or older and their first-degree relatives were subjected to the International Prostate Symptom Score (IPSS) and related examinations. Heritability was calculated according to the prevalence of the first-degree relatives in the case and control groups. Results The prevalence of BPH was 10.04%. Its prevalence increased with age, from 2.17% in men aged 40-44 years to 31.11% in men aged 80 years or older. The average volume of the prostate was 17.16 ± 7.96 mL, and the average IPSS was 5.89 ± 5.91. The analysis of the correlation between the associated risk factors and BPH revealed that prostatitis and a history of prostatic hyperplasia were significant factors. Obesity, smoking, drinking, diabetes, and hypertension were not correlated with BPH. Of the 94 first-degree relatives of the cases, 53 had BPH (56.38%); of the 106 first-degree relatives of the controls, five had BPH (4.72%). Heritability appeared to account for 40.48% of BPH cases. The heritability of incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia was 43.28, 71.37, 9.67, 5.67, 2.70, 53.36, and 19.12%, respectively. Conclusion The total prevalence of BPH in men aged 40 years or older in Zhengzhou's rural areas was 10.04%, and the heritability of prostatic hyperplasia was 40.48%.
- Published
- 2018
41. Differential analysis of chromatin accessibility and gene expression profiles identifies cis-regulatory elements in rat adipose and muscle
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Vishnu Nair, Mital Vasoya, Karyn A. Esser, Stuart C. Sealfon, Yongchao Ge, Gregory R. Smith, Venugopalan D. Nair, Collin M Douglas, and Hanna Pincas
- Subjects
Muscles ,Intron ,Adipose tissue ,ATAC-seq ,RNA-Seq ,Biology ,Regulatory Sequences, Nucleic Acid ,Chromatin ,Cell biology ,Rats ,Gene expression ,Genetics ,Animals ,Chromatin Immunoprecipitation Sequencing ,Transcriptome ,Transcription factor ,Gene - Abstract
Chromatin accessibility is a key factor influencing gene expression. We optimized the Omni-ATAC-seq protocol and used it together with RNA-seq to investigate cis-regulatory elements in rat white adipose and skeletal muscle, two tissues with contrasting metabolic functions. While promoter accessibility correlated with RNA expression, integration of the two datasets identified tissue-specific differentially accessible regions (DARs) that predominantly localized in intergenic and intron regions. DARs were mapped to differentially expressed (DE) genes enriched in distinct biological processes in each tissue. Randomly selected DE genes were validated by qPCR. Top enriched motifs in DARs predicted binding sites for transcription factors (TFs) showing tissue-specific up-regulation. The correlation between differential chromatin accessibility at a given TF binding motif and differential expression of target genes further supported the functional relevance of that motif. Our study identified cis-regulatory regions that likely play a major role in the regulation of tissue-specific gene expression in adipose and muscle.
- Published
- 2021
42. Contribution of Age, Brain Region, Mood Disorder Pathology, and Interindividual Factors on the Methylome of Human Microglia
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Qingkun Liu, Marjolein A. M. Sneeboer, Zhaoyu Wang, Fatemeh Haghighi, Yongchao Ge, Lot D. de Witte, Gijsje J. L. J. Snijders, Natalia Mendelev, and Marco P. Boks
- Subjects
Pathology ,medicine.medical_specialty ,Microglia ,Mood Disorders ,Central nervous system ,Brain ,Disease ,Methylation ,Biology ,DNA Methylation ,medicine.disease ,Transcriptome ,Epigenome ,medicine.anatomical_structure ,Differentially methylated regions ,Schizophrenia ,DNA methylation ,medicine ,Humans ,Biological Psychiatry - Abstract
Background Transcriptome studies have revealed age-, disease-, and region-associated microglial phenotypes reflecting changes in microglial function during development, aging, central nervous system homeostasis, and pathology. The molecular mechanisms that contribute to these transcriptomic changes are largely unknown. The aim of this study was to characterize the DNA methylation landscape of human microglia and factors that contribute to variations in the microglia methylome. We hypothesized that age and brain region would both have a large impact on DNA methylation in microglia. Methods Microglia from post-mortem brain tissue of four different brain regions of 22 donors, encompassing 1 patient with schizophrenia, 13 patients with mood disorder pathology, and 8 controls were isolated and assayed using genome-wide methylation array. Results We found that human microglial cells have a methylation profile distinct from bulk brain tissue and neurons, and age explained a considerable part of the variation. Additionally, we showed that interindividual factors had a much larger effect on the methylation landscape of microglia than brain region, that was also seen at the transcriptome level. In our explorative analysis we found various differentially methylated regions (DMRs) that were related to disease status (mood disorder versus control). This included DMRs that are linked to gene expression in microglia, as well as to myeloid cell function or neuropsychiatric disorders. Conclusions Although based on relatively small samples, these findings suggest that the methylation profile of microglia is responsive to interindividual variations, and thereby plays an important role in the heterogeneity of microglia observed at the transcriptome level.
- Published
- 2021
43. mRNA-1273 efficacy in a severe COVID-19 model: attenuated activation of pulmonary immune cells after challenge
- Author
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Stuart C. Sealfon, Yongchao Ge, Guillaume Stewart-Jones, Xi Chen, Chad E. Mire, Gregory R. Smith, Alexander Bukreyev, Barney S. Graham, Andrea Carfi, Colette Pietzsch, Carole Henry, Darin K. Edwards, Yuan Wang, Palaniappan Ramanathan, Bianca M. Nagata, Angela Woods, Sivakumar Periasamy, Pei Yong Shi, Michelle Meyer, LingZhi Ma, Aliza B. Rubenstein, Irene Ramos, Elena Zaslavsky, Minai Mahnaz, Ian N. Moore, Wan Sze Cheng, Kevin W. Bock, and Olga G. Troyanskaya
- Subjects
Lung ,Vaccine evaluation ,biology ,business.industry ,Lymphocyte ,Article ,Transcriptome ,Immune system ,medicine.anatomical_structure ,Immunity ,Immunology ,biology.protein ,Medicine ,Antibody ,business ,Homeostasis - Abstract
The mRNA-1273 vaccine was recently determined to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from interim Phase 3 results. Human studies, however, cannot provide the controlled response to infection and complex immunological insight that are only possible with preclinical studies. Hamsters are the only model that reliably exhibit more severe SARS-CoV-2 disease similar to hospitalized patients, making them pertinent for vaccine evaluation. We demonstrate that prime or prime-boost administration of mRNA-1273 in hamsters elicited robust neutralizing antibodies, ameliorated weight loss, suppressed SARS-CoV-2 replication in the airways, and better protected against disease at the highest prime-boost dose. Unlike in mice and non-human primates, mRNA-1273- mediated immunity was non-sterilizing and coincided with an anamnestic response. Single-cell RNA sequencing of lung tissue permitted high resolution analysis which is not possible in vaccinated humans. mRNA-1273 prevented inflammatory cell infiltration and the reduction of lymphocyte proportions, but enabled antiviral responses conducive to lung homeostasis. Surprisingly, infection triggered transcriptome programs in some types of immune cells from vaccinated hamsters that were shared, albeit attenuated, with mock-vaccinated hamsters. Our results support the use of mRNA-1273 in a two-dose schedule and provides insight into the potential responses within the lungs of vaccinated humans who are exposed to SARS-CoV-2.
- Published
- 2021
44. SARS-CoV-2 Seropositivity among US Marine Recruits Attending Basic Training, United States, Spring-Fall 2020
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Alessandra Soares-Schanoski, Dawn L. Weir, Andrew G. Letizia, Sindhu Vangeti, Carl Goforth, Rhonda A. Lizewski, Nada Marjanovic, Yongchao Ge, Irene Ramos, Stephen E. Lizewski, and Stuart C. Sealfon
- Subjects
Male ,Epidemiology ,Cross-sectional study ,lcsh:Medicine ,law.invention ,0302 clinical medicine ,law ,Seroepidemiologic Studies ,Pandemic ,Medicine ,030212 general & internal medicine ,Young adult ,SARS-CoV-2 Seropositivity among US Marine Recruits Attending Basic Training, United States, Spring–Fall 2020 ,seroprevalence ,Age Factors ,Dispatch ,Military personnel ,Infectious Diseases ,Military Personnel ,coronavirus disease ,Quarantine ,Female ,severe acute respiratory syndrome coronavirus 2 ,Microbiology (medical) ,young adults ,medicine.medical_specialty ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Military Health Services ,030231 tropical medicine ,military recruits ,lcsh:Infectious and parasitic diseases ,COVID-19 Serological Testing ,03 medical and health sciences ,Young Adult ,respiratory infections ,Seroprevalence ,Humans ,lcsh:RC109-216 ,viruses ,Personnel Selection ,Demography ,business.industry ,SARS-CoV-2 ,Public health ,lcsh:R ,COVID-19 ,Military Health ,United States ,zoonoses ,Cross-Sectional Studies ,business - Abstract
In a study of US Marine recruits, seroprevalence of severe acute respiratory syndrome coronavirus 2 IgG was 9.0%. Hispanic and non-Hispanic Black participants and participants from states affected earlier in the pandemic had higher seropositivity rates. These results suggest the need for targeted public health strategies among young adults at increased risk for infection.
- Published
- 2021
45. Attenuated activation of pulmonary immune cells in mRNA-1273-vaccinated hamsters after SARS-CoV-2 infection
- Author
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Barney S. Graham, Angela Woods, Pei Yong Shi, Ian N. Moore, Kevin W. Bock, Xi Chen, Stuart C. Sealfon, Irene Ramos, Guillaume Stewart-Jones, Chad E. Mire, Carole Henry, Palaniappan Ramanathan, Alexander Bukreyev, Colette Pietzsch, Aliza B. Rubenstein, Elena Zaslavsky, Olga G. Troyanskaya, Sivakumar Periasamy, Bianca M. Nagata, Mahnaz Minai, Michelle Meyer, Gregory R. Smith, Darin K. Edwards, Andrea Carfi, Wan Sze Cheng, LingZhi Ma, Yuan Wang, and Yongchao Ge
- Subjects
COVID-19 Vaccines ,Vaccine evaluation ,Lymphocyte ,Immunization, Secondary ,Antibodies, Viral ,Lymphocyte Activation ,Virus Replication ,Immune system ,medicine ,Animals ,Humans ,Lung ,biology ,Mesocricetus ,business.industry ,SARS-CoV-2 ,COVID-19 ,General Medicine ,Acquired immune system ,biology.organism_classification ,Antibodies, Neutralizing ,Disease Models, Animal ,medicine.anatomical_structure ,Viral replication ,Immunology ,biology.protein ,Female ,Antibody ,Single-Cell Analysis ,business ,2019-nCoV Vaccine mRNA-1273 ,Research Article - Abstract
The mRNA-1273 vaccine is effective against SARS-CoV-2 and was granted emergency use authorization by the FDA. Clinical studies, however, cannot provide the controlled response to infection and complex immunological insight that are only possible with preclinical studies. Hamsters are the only model that reliably exhibits severe SARS-CoV-2 disease similar to that in hospitalized patients, making them pertinent for vaccine evaluation. We demonstrate that prime or prime-boost administration of mRNA-1273 in hamsters elicited robust neutralizing antibodies, ameliorated weight loss, suppressed SARS-CoV-2 replication in the airways, and better protected against disease at the highest prime-boost dose. Unlike in mice and nonhuman primates, low-level virus replication in mRNA-1273-vaccinated hamsters coincided with an anamnestic response. Single-cell RNA sequencing of lung tissue permitted high-resolution analysis that is not possible in vaccinated humans. mRNA-1273 prevented inflammatory cell infiltration and the reduction of lymphocyte proportions, but enabled antiviral responses conducive to lung homeostasis. Surprisingly, infection triggered transcriptome programs in some types of immune cells from vaccinated hamsters that were shared, albeit attenuated, with mock-vaccinated hamsters. Our results support the use of mRNA-1273 in a 2-dose schedule and provide insight into the potential responses within the lungs of vaccinated humans who are exposed to SARS-CoV-2.
- Published
- 2021
46. SARS-CoV-2 Seropositivity and Subsequent Infection Risk in Healthy Young Adults: A Prospective Cohort Study
- Author
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Carl Goforth, Michael Termini, Daniel Stadlbauer, Stephen E. Lizewski, Alessandra Soares-Schanoski, Victor A. Sugiharto, Danielle M. Parent, Edgar Nunez, Rhonda A. Lizewski, Yongchao Ge, Clare M. Miller, Megan A. Schilling, Sindhu Vangeti, Florian Krammer, Alexander Bukreyev, Venugopalan D. Nair, Chad K. Porter, Andrew G. Letizia, Hua Wei Chen, Mary-Catherine George, Ernesto Santa Ana, Nada Marjanovic, Peifang Sun, Stuart C. Sealfon, Sagie Mofsowitz, Natalia Kuzmina, Russell P. Tracy, Preeti Bharaj, Franca R. Jones, Daniel Ewing, Irene Ramos, Dawn L. Weir, Jan Marayag, and William D. Graham
- Subjects
medicine.medical_specialty ,biology ,business.industry ,Institutional review board ,Rate ratio ,law.invention ,Serology ,Titer ,law ,Immunity ,Internal medicine ,Quarantine ,biology.protein ,Medicine ,Population study ,Antibody ,Young adult ,business ,Prospective cohort study ,Viral load - Abstract
Background: The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subsequent infection among seropositive young adults was studied prospectively. Methods: The study population comprised 3,249 predominantly male, 18-20-year-old Marine recruits. Upon arrival at a Marine-supervised two-week quarantine, participants were assessed for baseline SARS-CoV-2 IgG seropositivity, defined as a 1:150 dilution or greater on receptor binding domain and full-length spike protein enzyme-linked immunosorbent (ELISA) assays. SARS-CoV-2 infection was assessed by PCR at initiation, middle and end of the quarantine. After appropriate exclusions, including participants with a positive PCR during quarantine, we performed three biweekly PCR tests in both seropositive and in seronegative groups once recruits left quarantine and entered basic training and baseline neutralizing antibody titers on all subsequently infected seropositive and selected seropositive uninfected participants. Findings: Among 189 seropositive participants, 19 (10.1%) had at least one positive PCR test for SARS-CoV-2 during the six-week follow-up (1.1 cases per person-year). In contrast, 1,079 (48.0%) of the 2,247 seronegative participants tested positive (6.2 cases per person-year). The incidence rate ratio was 0.18 (95% CI 0.11-0.28, p
- Published
- 2021
47. DNA Methylation Patterns of Chronic Explosive Breaching in U.S. Military Warfighters
- Author
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Gary H. Kamimori, Christina R. LaValle, Angela M. Boutté, Walter Carr, Zhaoyu Wang, Yongchao Ge, Jeffrey Nemes, Fatemeh Haghighi, and Caroline Wilson
- Subjects
0301 basic medicine ,Bioinformatics ,lcsh:RC346-429 ,breacher ,03 medical and health sciences ,0302 clinical medicine ,medicine ,pain ,Epigenetics ,tinnitus ,sleep ,lcsh:Neurology. Diseases of the nervous system ,Original Research ,DNA methylation ,epigenetics ,business.industry ,Chronic pain ,medicine.disease ,blast exposure ,Sleep in non-human animals ,030104 developmental biology ,Differentially methylated regions ,Neurology ,Etiology ,Neurology (clinical) ,medicine.symptom ,Headaches ,business ,030217 neurology & neurosurgery ,Tinnitus - Abstract
Background: Injuries from exposure to explosions rose dramatically during the Iraq and Afghanistan wars, which motivated investigation of blast-related neurotrauma. We have undertaken human studies involving military “breachers” —exposed to controlled, low-level blast during a 3-days explosive breaching course.Methods: We screened epigenetic profiles in peripheral blood samples from 59 subjects (in two separate U.S. Military training sessions) using Infinium MethylationEPIC BeadChips. Participants had varying numbers of exposures to blast over their military careers (empirically defined as high ≥ 40, and conversely, low < 39 breaching exposures). Daily self-reported physiological symptoms were recorded. Tinnitus, memory problems, headaches, and sleep disturbances are most frequently reported.Results: We identified 14 significantly differentially methylated regions (DMRs) within genes associated with cumulative blast exposure in participants with high relative to low cumulative blast exposure. Notably, NTSR1 and SPON1 were significantly differentially methylated in high relative to low blast exposed groups, suggesting that sleep dysregulation may be altered in response to chronic cumulative blast exposure. In comparing lifetime blast exposure at baseline (prior to exposure in current training), and top associated symptoms, we identified significant DMRs associated with tinnitus, sleep difficulties, and headache. Notably, we identified KCNN3, SOD3, MUC4, GALR1, and WDR45B, which are implicated in auditory function, as differentially methylated associated with self-reported tinnitus. These findings suggest neurobiological mechanisms behind auditory injuries in our military warfighters and are particularly relevant given tinnitus is not only a primary disability among veterans, but has also been demonstrated in active duty medical records for populations exposed to blast in training. Additionally, we found that differentially methylated regions associated with the genes CCDC68 and COMT track with sleep difficulties, and those within FMOD and TNXB track with pain and headache.Conclusion: Sleep disturbances, as well as tinnitus and chronic pain, are widely reported in U.S. military service members and veterans. As we have previously demonstrated, DNA methylation encapsulates lifetime exposure to blast. The current data support previous findings and recapitulate transcriptional regulatory alterations in genes involved in sleep, auditory function, and pain. These data uncovered novel epigenetic and transcriptional regulatory mechanism underlying the etiological basis of these symptoms.
- Published
- 2020
48. Sedentary and Trained Older Men Have Distinct Circulating Exosomal microRNA Profiles at Baseline and in Response to Acute Exercise
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Stuart C. Sealfon, Hanna Pincas, Martin J. Walsh, Yongchao Ge, Nitish Seenarine, Mary Anne S. Amper, SiDe Li, Paul M. Coen, Venugopalan D. Nair, Bret H. Goodpaster, and Nimisha Jain
- Subjects
0301 basic medicine ,Anabolism ,Physiology ,Acute aerobic exercise ,lcsh:Physiology ,Older population ,03 medical and health sciences ,0302 clinical medicine ,insulin growth factor-1 signaling ,Regular exercise ,Physiology (medical) ,microRNA ,regular endurance training ,Medicine ,Aerobic exercise ,Original Research ,lcsh:QP1-981 ,business.industry ,aging ,microRNA profiling ,Skeletal muscle ,plasma exosomes ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cardiac hypertrophy ,Sedentary group ,business - Abstract
Exercise has multi-systemic benefits and attenuates the physiological impairments associated with aging. Emerging evidence suggests that circulating exosomes mediate some of the beneficial effects of exercise via the transfer of microRNAs between tissues. However, the impact of regular exercise and acute exercise on circulating exosomal microRNAs (exomiRs) in older populations remains unknown. In the present study, we analyzed circulating exomiR expression in endurance-trained elderly men (n = 5) and age-matched sedentary males (n = 5) at baseline (Pre), immediately after a forty minute bout of aerobic exercise on a cycle ergometer (Post), and three hours after this acute exercise (3hPost). Following the isolation and enrichment of exosomes from plasma, exosome-enriched preparations were characterized and exomiR levels were determined by sequencing. The effect of regular exercise on circulating exomiRs was assessed by comparing the baseline expression levels in the trained and sedentary groups. The effect of acute exercise was determined by comparing baseline and post-training expression levels in each group. Regular exercise resulted in significantly increased baseline expression of three exomiRs (miR-486-5p, miR-215-5p, miR-941) and decreased expression of one exomiR (miR-151b). Acute exercise altered circulating exomiR expression in both groups. However, exomiRs regulated by acute exercise in the trained group (7 miRNAs at Post and 8 at 3hPost) were distinct from those in the sedentary group (9 at Post and 4 at 3hPost). Pathway analysis prediction and reported target validation experiments revealed that the majority of exercise-regulated exomiRs are targeting genes that are related to IGF-1 signaling, a pathway involved in exercise-induced muscle and cardiac hypertrophy. The immediately post-acute exercise exomiR signature in the trained group correlates with activation of IGF-1 signaling, whereas in the sedentary group it is associated with inhibition of IGF-1 signaling. While further validation is needed, including measurements of IGF-1/IGF-1 signaling in blood or skeletal muscle, our results suggest that training status may counteract age-related anabolic resistance by modulating circulating exomiR profiles both at baseline and in response to acute exercise.
- Published
- 2020
49. SAT-298 Integrative Single-Cell Transcriptomic and Epigenomic Landscape of Mouse Anterior Pituitary Cell Types
- Author
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Judith L Turgeon, Joseph R. Nery, Andrew Alridge, Anna Bartlett, Frederique Ruf-Zamojski, Mika Moriwaki, Joseph R. Ecker, Yongchao Ge, Stuart C. Sealfon, Corrine K. Welt, Luisina Ongaro Gambino, Hanqing Liu, Rosa Castanon, Natalia Mendelev, Gauthier Schang, Venugopalan D. Nair, German Nudelman, Xiang Zhou, Hanna Pincas, Gwen V. Childs, Daniel J. Bernard, Gregory R. Smith, Michel Zamojski, Chirine Toufaily, and Angela K. Odle
- Subjects
Cell type ,endocrine system ,Endocrinology, Diabetes and Metabolism ,Cell ,Biology ,Hypothalamic-Pituitary Development and Function ,Cell biology ,Transcriptome ,medicine.anatomical_structure ,Neuroendocrinology and Pituitary ,Anterior pituitary ,medicine ,AcademicSubjects/MED00250 ,Epigenomics - Abstract
The pituitary gland is a critical regulator of the neuroendocrine system. To further our understanding of the classification, cellular heterogeneity, and regulatory landscape of pituitary cell types, we performed and computationally integrated single cell (SC)/single nucleus (SN) resolution experiments capturing RNA expression, chromatin accessibility, and DNA methylation state from mouse dissociated whole pituitaries. Both SC and SN transcriptome analysis and promoter accessibility identified the five classical hormone-producing cell types (somatotropes, gonadotropes (GT), lactotropes, thyrotropes, and corticotropes). GT cells distinctively expressed transcripts for Cga, Fshb, Lhb, Nr5a1, and Gnrhr in SC RNA-seq and SN RNA-seq. This was matched in SN ATAC-seq with GTs specifically showing open chromatin at the promoter regions for the same genes. Similarly, the other classically defined anterior pituitary cells displayed transcript expression and chromatin accessibility patterns characteristic of their own cell type. This integrated analysis identified additional cell-types, such as a stem cell cluster expressing transcripts for Sox2, Sox9, Mia, and Rbpms, and a broadly accessible chromatin state. In addition, we performed bulk ATAC-seq in the LβT2b gonadotrope-like cell line. While the FSHB promoter region was closed in the cell line, we identified a region upstream of Fshb that became accessible by the synergistic actions of GnRH and activin A, and that corresponded to a conserved region identified by a polycystic ovary syndrome (PCOS) single nucleotide polymorphism (SNP). Although this locus appears closed in deep sequencing bulk ATAC-seq of dissociated mouse pituitary cells, SN ATAC-seq of the same preparation showed that this site was specifically open in mouse GT, but closed in 14 other pituitary cell type clusters. This discrepancy highlighted the detection limit of a bulk ATAC-seq experiment in a subpopulation, as GT represented ~5% of this dissociated anterior pituitary sample. These results identified this locus as a candidate for explaining the dual dependence of Fshb expression on GnRH and activin/TGFβ signaling, and potential new evidence for upstream regulation of Fshb. The pituitary epigenetic landscape provides a resource for improved cell type identification and for the investigation of the regulatory mechanisms driving cell-to-cell heterogeneity. Additional authors not listed due to abstract submission restrictions: N. Seenarine, M. Amper, N. Jain (ISMMS).
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- 2020
50. Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise
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James A. Sanford, Christopher D. Nogiec, Malene E. Lindholm, Joshua N. Adkins, David Amar, Surendra Dasari, Jonelle K. Drugan, Facundo M. Fernández, Shlomit Radom-Aizik, Simon Schenk, Michael P. Snyder, Russell P. Tracy, Patrick Vanderboom, Scott Trappe, Martin J. Walsh, Charles R. Evans, Facundo M. Fernandez, Yafeng Li, Lyl Tomlinson, D. Lee Alekel, Iddil Bekirov, Amanda T. Boyce, Josephine Boyington, Jerome L. Fleg, Lyndon J.O. Joseph, Maren R. Laughlin, Padma Maruvada, Stephanie A. Morris, Joan A. McGowan, Concepcion Nierras, Vinay Pai, Charlotte Peterson, Ed Ramos, Mary C. Roary, John P. Williams, Ashley Xia, Elaine Cornell, Jessica Rooney, Michael E. Miller, Walter T. Ambrosius, Scott Rushing, Cynthia L. Stowe, W. Jack Rejeski, Barbara J. Nicklas, Marco Pahor, Ching-ju Lu, Todd Trappe, Toby Chambers, Ulrika Raue, Bridget Lester, Bryan C. Bergman, David H. Bessesen, Catherine M. Jankowski, Wendy M. Kohrt, Edward L. Melanson, Kerrie L. Moreau, Irene E. Schauer, Robert S. Schwartz, William E. Kraus, Cris A. Slentz, Kim M. Huffman, Johanna L. Johnson, Leslie H. Willis, Leslie Kelly, Joseph A. Houmard, Gabriel Dubis, Nick Broskey, Bret H. Goodpaster, Lauren M. Sparks, Paul M. Coen, Dan M. Cooper, Fadia Haddad, Tuomo Rankinen, Eric Ravussin, Neil Johannsen, Melissa Harris, John M. Jakicic, Anne B. Newman, Daniel D. Forman, Erin Kershaw, Renee J. Rogers, Bradley C. Nindl, Lindsay C. Page, Maja Stefanovic-Racic, Susan L. Barr, Blake B. Rasmussen, Tatiana Moro, Doug Paddon-Jones, Elena Volpi, Heidi Spratt, Nicolas Musi, Sara Espinoza, Darpan Patel, Monica Serra, Jonathan Gelfond, Aisling Burns, Marcas M. Bamman, Thomas W. Buford, Gary R. Cutter, Sue C. Bodine, Karyn Esser, Rodger P. Farrar, Laurie J. Goodyear, Michael F. Hirshman, Brent G. Albertson, Wei-Jun Qian, Paul Piehowski, Marina A. Gritsenko, Matthew E. Monore, Vladislav A. Petyuk, Jason E. McDermott, Joshua N. Hansen, Chelsea Hutchison, Samuel Moore, David A. Gaul, Clary B. Clish, Julian Avila-Pacheco, Courtney Dennis, Manolis Kellis, Steve Carr, Pierre M. Jean-Beltran, Hasmik Keshishian, D.R. Mani, Karl Clauser, Karsten Krug, Charlie Mundorff, Cadence Pearce, Anna A. Ivanova, Eric A. Ortlund, Kristal Maner-Smith, Karan Uppal, Tiantian Zhang, Stuart C. Sealfon, Elena Zaslavsky, Venugopalan Nair, SiDe Li, Nimisha Jain, YongChao Ge, Yifei Sun, German Nudelman, Frederique Ruf-zamojski, Gregory Smith, Nhanna Pincas, Aliza Rubenstein, Mary Anne Amper, Nitish Seenarine, Tuuli Lappalainen, Ian R. Lanza, K. Sreekumaran Nair, Katherine Klaus, Stephen B. Montgomery, Kevin S. Smith, Nicole R. Gay, Bingqing Zhao, Chia-Jiu Hung, Navid Zebarjadi, Brunilda Balliu, Laure Fresard, Charles F. Burant, Jun Z. Li, Maureen Kachman, Tanu Soni, Alexander B. Raskind, Robert Gerszten, Jeremy Robbins, Olga Ilkayeva, Michael J. Muehlbauer, Christopher B. Newgard, Euan A. Ashley, Matthew T. Wheeler, David Jimenez-Morales, Archana Raja, Karen P. Dalton, Jimmy Zhen, Young Suk Kim, Jeffrey W. Christle, Shruti Marwaha, Elizabeth T. Chin, Steven G. Hershman, Trevor Hastie, Robert Tibshirani, and Manuel A. Rivas
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Physical activity ,Disease ,Health benefits ,Biology ,Animals ,Child ,Exercise ,Female ,Humans ,Middle Aged ,Oxygen Consumption ,Physical Endurance ,Research Design ,Young Adult ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,medicine ,Exercise physiology ,Organ system ,030304 developmental biology ,0303 health sciences ,Extramural ,Resistance training ,030217 neurology & neurosurgery - Abstract
Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease.
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- 2020
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