8 results on '"Hao, Yuhan"'
Search Results
2. A RORγt + cell instructs gut microbiota-specific T reg cell differentiation.
- Author
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Kedmi R, Najar TA, Mesa KR, Grayson A, Kroehling L, Hao Y, Hao S, Pokrovskii M, Xu M, Talbot J, Wang J, Germino J, Lareau CA, Satpathy AT, Anderson MS, Laufer TM, Aifantis I, Bartleson JM, Allen PM, Paidassi H, Gardner JM, Stoeckius M, and Littman DR
- Subjects
- Dendritic Cells immunology, Homeostasis, Immunity, Innate, Integrin alphaV metabolism, Receptors, CCR7 metabolism, Th17 Cells immunology, Transforming Growth Factor beta metabolism, Antigen Presentation immunology, Antigen-Presenting Cells cytology, Antigen-Presenting Cells immunology, Cell Differentiation, Gastrointestinal Microbiome immunology, Nuclear Receptor Subfamily 1, Group F, Member 3 metabolism, T-Lymphocytes, Regulatory cytology, T-Lymphocytes, Regulatory immunology
- Abstract
The mutualistic relationship of gut-resident microbiota and the host immune system promotes homeostasis that ensures maintenance of the microbial community and of a largely non-aggressive immune cell compartment
1,2 . The consequences of disturbing this balance include proximal inflammatory conditions, such as Crohn's disease, and systemic illnesses. This equilibrium is achieved in part through the induction of both effector and suppressor arms of the adaptive immune system. Helicobacter species induce T regulatory (Treg ) and T follicular helper (TFH ) cells under homeostatic conditions, but induce inflammatory T helper 17 (TH 17) cells when induced Treg (iTreg ) cells are compromised3,4 . How Helicobacter and other gut bacteria direct T cells to adopt distinct functions remains poorly understood. Here we investigated the cells and molecular components required for iTreg cell differentiation. We found that antigen presentation by cells expressing RORγt, rather than by classical dendritic cells, was required and sufficient for induction of Treg cells. These RORγt+ cells-probably type 3 innate lymphoid cells and/or Janus cells5 -require the antigen-presentation machinery, the chemokine receptor CCR7 and the TGFβ activator αv integrin. In the absence of any of these factors, there was expansion of pathogenic TH 17 cells instead of iTreg cells, induced by CCR7-independent antigen-presenting cells. Thus, intestinal commensal microbes and their products target multiple antigen-presenting cells with pre-determined features suited to directing appropriate T cell differentiation programmes, rather than a common antigen-presenting cell that they endow with appropriate functions., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2022
- Full Text
- View/download PDF
3. Case control study comparing the HPV genome in patients with oral cavity squamous cell carcinoma to normal patients using metagenomic shotgun sequencing.
- Author
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Ganly I, Pei Z, Hao Y, Ma Y, Rosenthal M, Wu Z, Migliacci J, Huang B, Katabi N, Tseng W, Brown S, Tang YW, and Yang L
- Subjects
- Aged, Case-Control Studies, Female, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Alphapapillomavirus genetics, Carcinoma, Squamous Cell virology, Metagenome, Mouth Neoplasms virology
- Abstract
The aim of this study was to carry out a case control study comparing the HPV genome in patients with oral cavity squamous cell carcinoma (OC-SCC) to normal patients using metagenomic shotgun sequencing. We recruited 50 OC-SCC cases which were then matched with a control patient by age, gender, race, smoking status and alcohol status. DNA was extracted from oral wash samples from all patients and whole genome shotgun sequencing performed. The raw sequence data was cleaned, reads aligned with the human genome (GRCH38), nonhuman reads identified and then HPV genotypes identified using HPViewer. In the 50 patients with OC-SCC, the most common subsite was tongue in 26 (52%). All patients were treated with primary resection and neck dissection. All but 2 tumors were negative on p16 immunohistochemistry. There were no statistically significant differences between the cases and controls in terms of gender, age, race/ethnicity, alcohol drinking, and cigarette smoking. There was no statistically significant difference between the cancer samples and control samples in the nonhuman DNA reads (medians 4,228,072 vs. 5,719,715, P value = 0.324). HPV was detected in 5 cases (10%) of OC-SCC (genotypes 10, 16, 98) but only 1 tumor sample (genotype 16) yielded a high number of reads to suggest a role in the etiology of OC-SCC. HPV was detected in 4 control patients (genotypes 16, 22, 76, 200) but all had only 1-2 HPV reads per human genome. Genotypes of HPV are rarely found in patients with oral cancer.
- Published
- 2021
- Full Text
- View/download PDF
4. Author Correction: Parkinson's disease and bacteriophages as its overlooked contributors.
- Author
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Tetz G, Brown SM, Hao Y, and Tetz V
- Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
- Published
- 2020
- Full Text
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5. Mitochondrial somatic mutations and the lack of viral genomic variation in recurrent respiratory papillomatosis.
- Author
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Hao Y, Ruiz R, Yang L, Neto AG, Amin MR, Kelly D, Achlatis S, Roof S, Bing R, Kannan K, Brown SM, Pei Z, and Branski RC
- Subjects
- Adult, DNA, Viral genetics, Female, Genetic Variation genetics, Humans, Male, Middle Aged, Mouth virology, Multiplex Polymerase Chain Reaction, Mutation genetics, Papillomavirus Infections diagnosis, Papillomavirus Infections genetics, Phylogeny, Polymorphism, Single Nucleotide genetics, Respiratory Tract Infections diagnosis, Respiratory Tract Infections genetics, Genome, Viral genetics, Human papillomavirus 11 genetics, Human papillomavirus 6 genetics, Mitochondria genetics, Papillomavirus Infections virology, Respiratory Tract Infections virology
- Abstract
Recurrent Respiratory Papillomatosis (RRP) is a rare disease of the aerodigestive tract caused by the Human Papilloma Virus (HPV) that manifests as profoundly altered phonatory and upper respiratory anatomy. Current therapies are primarily symptomatic; enhanced insight regarding disease-specific biology of RRP is critical to improved therapeutics for this challenging population. Multiplex PCR was performed on oral rinses collected from twenty-three patients with adult-onset RRP every three months for one year. Twenty-two (95.6%) subjects had an initial HPV positive oral rinse. Of those subjects, 77.2% had an additional positive oral rinse over 12 months. A subset of rinses were then compared to tissue samples in the same patient employing HPViewer to determine HPV subtype concordance. Multiple HPV copies (60-787 per human cell) were detected in RRP tissue in each patient, but a single dominant HPV was found in individual samples. These data confirm persistent oral HPV infection in the majority of patients with RRP. In addition, three novel HPV6 isolates were found and identical HPV strains, at very low levels, were identified in oral rinses in two patients suggesting potential HPV subtype concordance. Finally, somatic heteroplasmic mtDNA mutations were observed in RRP tissue with 1.8 mutations per sample and two nonsynonymous variants. These data provide foundational insight into both the underlying pathophysiology of RRP, but also potential targets for intervention in this challenging patient cohort.
- Published
- 2019
- Full Text
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6. Type 1 Diabetes: an Association Between Autoimmunity, the Dynamics of Gut Amyloid-producing E. coli and Their Phages.
- Author
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Tetz G, Brown SM, Hao Y, and Tetz V
- Subjects
- Child, Preschool, Coliphages immunology, Diabetes Mellitus, Type 1 metabolism, Diabetes Mellitus, Type 1 pathology, Escherichia coli immunology, Humans, Infant, Infant, Newborn, Longitudinal Studies, Prospective Studies, Amyloid metabolism, Autoimmunity immunology, Coliphages metabolism, Diabetes Mellitus, Type 1 etiology, Escherichia coli metabolism, Gastrointestinal Microbiome immunology
- Abstract
The etiopathogenesis of type 1 diabetes (T1D), a common autoimmune disorder, is not completely understood. Recent studies suggested the gut microbiome plays a role in T1D. We have used public longitudinal microbiome data from T1D patients to analyze amyloid-producing bacterial composition and found a significant association between initially high amyloid-producing Escherichia coli abundance, subsequent E. coli depletion prior to seroconversion, and T1D development. In children who presented seroconversion or developed T1D, we observed an increase in the E. coli phage/E. coli ratio prior to E. coli depletion, suggesting that the decrease in E. coli was due to prophage activation. Evaluation of the role of phages in amyloid release from E. coli biofilms in vitro suggested an indirect role of the bacterial phages in the modulation of host immunity. This study for the first time suggests that amyloid-producing E. coli, their phages, and bacteria-derived amyloid might be involved in pro-diabetic pathway activation in children at risk for T1D.
- Published
- 2019
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- View/download PDF
7. Parkinson's disease and bacteriophages as its overlooked contributors.
- Author
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Tetz G, Brown SM, Hao Y, and Tetz V
- Subjects
- Bacteria genetics, Bacteria isolation & purification, Bacteria metabolism, Bacteriophages genetics, Case-Control Studies, DNA, Bacterial chemistry, DNA, Bacterial isolation & purification, DNA, Bacterial metabolism, DNA, Viral chemistry, DNA, Viral isolation & purification, DNA, Viral metabolism, Dopamine metabolism, Feces microbiology, Humans, Microbiota, Parkinson Disease virology, Principal Component Analysis, Bacteriophages isolation & purification, Feces virology, Parkinson Disease pathology
- Abstract
Recent studies suggest that alterations in the gut phagobiota may contribute to pathophysiological processes in mammals; however, the association of bacteriophage community structure with Parkinson's disease (PD) has not been yet characterized. Towards this end, we used a published dataset to analyse bacteriophage composition and determine the phage/bacteria ratio in faecal samples from drug-naive PD patients and healthy participants. Our analyses revealed significant alterations in the representation of certain bacteriophages in the phagobiota of PD patients. We identified shifts of the phage/bacteria ratio in lactic acid bacteria known to produce dopamine and regulate intestinal permeability, which are major factors implicated in PD pathogenesis. Furthermore, we observed the depletion of Lactococcus spp. in the PD group, which was most likely due to the increase of lytic c2-like and 936-like lactococcal phages frequently present in dairy products. Our findings add bacteriophages to the list of possible factors associated with the development of PD, suggesting that gut phagobiota composition may serve as a diagnostic tool as well as a target for therapeutic intervention, which should be confirmed in further studies. Our results open a discussion on the role of environmental phages and phagobiota composition in health and disease.
- Published
- 2018
- Full Text
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8. Cryo-EM structure of human ATR-ATRIP complex.
- Author
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Rao Q, Liu M, Tian Y, Wu Z, Hao Y, Song L, Qin Z, Ding C, Wang HW, Wang J, and Xu Y
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- Adaptor Proteins, Signal Transducing genetics, Ataxia Telangiectasia Mutated Proteins antagonists & inhibitors, Ataxia Telangiectasia Mutated Proteins genetics, Carrier Proteins metabolism, Chromatography, Affinity, Chromatography, Gel, Cryoelectron Microscopy, DNA Damage, DNA-Binding Proteins genetics, Humans, Isoxazoles metabolism, Mutation, Nuclear Proteins metabolism, Phosphorylation, Protein Binding, Protein Conformation, alpha-Helical, Protein Folding, Protein Kinases metabolism, Protein Multimerization, Pyrazines metabolism, Signal Transduction, TOR Serine-Threonine Kinases chemistry, Adaptor Proteins, Signal Transducing chemistry, Adaptor Proteins, Signal Transducing metabolism, Ataxia Telangiectasia Mutated Proteins chemistry, Ataxia Telangiectasia Mutated Proteins metabolism, DNA-Binding Proteins chemistry, DNA-Binding Proteins metabolism
- Abstract
ATR (ataxia telangiectasia-mutated and Rad3-related) protein kinase and ATRIP (ATR-interacting protein) form a complex and play a critical role in response to replication stress and DNA damage. Here, we determined the cryo-electron microscopy (EM) structure of the human ATR-ATRIP complex at 4.7 Å resolution and built an atomic model of the C-terminal catalytic core of ATR (residues 1 521-2 644) at 3.9 Å resolution. The complex adopts a hollow "heart" shape, consisting of two ATR monomers in distinct conformations. The EM map for ATRIP reveals 14 HEAT repeats in an extended "S" shape. The conformational flexibility of ATR allows ATRIP to properly lock the N-termini of the two ATR monomers to favor ATR-ATRIP complex formation and functional diversity. The isolated "head-head" and "tail-tail" each adopts a pseudo 2-fold symmetry. The catalytic pockets face outward and substrate access is not restricted by inhibitory elements. Our studies provide a structural basis for understanding the assembly of the ATR-ATRIP complex and a framework for characterizing ATR-mediated DNA repair pathways.
- Published
- 2018
- Full Text
- View/download PDF
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