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NK/CTL granzymes mediate immune surveillance against tumors and viruses

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NK/CTL granzymes mediate immune surveillance against tumors ...

A DNA Aptamer Based Method for Detection of SARS-CoV-2 Nucleocapsid Protein

第八届全国免疫学学术大会

作者： Zusen Fan CAS Key lab for infection and immunity Institute of Biophysics Chinese Academy of Sciences

Cytotoxic lymphocytes are major players that eliminate transformed tumor cells or cells infected with intracellular *** this process, pore-forming protein perforin and cytotoxic protease granzymes(Gzms) are released from their granules into the immunological synapse formed between cytotoxic cells and their *** are a highly conserved set of serine *** they are delivered into target cells by perforin, they can cleave cellular or viral proteins, leading to the destruction of target cells or inhibition of viral *** express five Gzms(A, B, K, H, and M).Because Gzm A and B are the most abundant proteases of the Gzm family in humans and mice, their functions have been extensively ***, we have defined some roles of orphan Gzms(H, K, and M) against tumors and *** demonstrated that Gzm K targets the SET complex to initiate caspase-independent cell *** K can induce the rapid generation of reactive oxygen species( ROS) through a Bid-dependent *** K also cleaves the valosincontaining protein(VCP) to destroy the E R-associated degradation(E RAD) pathway, resulting in E R stress ofthe target *** also found that Gzm K proteolyzes the tumor suppressor p53 to generate three pro-apoptotic segments that potentially increase elimination of target tumor ***, Gzm K can inhibit replication of influenza A virus through proteolysis of the importin α1/β dimer to disrupt transportation of the viral NP to the *** also demonstrated that Gzm M and Gzm H induce caspase-dependent cell death with different mechanisms and defined their crystal ***, we found that lymphokine-activated killer(LAK) cells inhibit HBV replication in HepG2.2.15 cells without cytolysis of target *** H participates in the clearance of HBV virus via cleavage of the HBx *** transfer of Gzm H-expressing NK cells into an HBV mouse model facilitates HBV ***, low Gzm H ex

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Virologica Sinica 2020年第3期35卷 351-354页

作者： Zhiqiang Chen Qihan Wu Jing Chen Xiaohua Ni Jianfeng Dai Institutes of Biology and Medical Sciences Jiangsu Key Laboratory of Infection and ImmunitySoochow UniversitySuzhou 215123China Department of Nuclear Medicine The First Affiliated Hospital of Soochow UniversitySuzhou 215006China NHC Key lab of Reproduction Regulation(Shanghai Institute of Planned Parenthood Research) Fudan UniversityShanghai 200035China

Dear Editor,Since December 2019, the outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) induced human disease, the coronavirus disease 2019(COVID-19),has been reported in more than 200 countries a... 详细信息

关键词： al. acute respiratory

The Ring Vortex: Concepts for a Novel Complex Flow Phantom for Medical Imaging

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Open Journal of Medical Imaging 2017年第1期7卷 28-41页

作者： Simone Ferrari Simone Ambrogio Adrian Walker Prashant Verma Andrew J. Narracott Iain Wilkinson John W. Fenner Medical Physics Mathematical Modelling in Medicine Group Department of Infection Immunity and Cardiovascular Disease University of Sheffield Sheffield UK Insigneo Institute for In Silico Medicine University of Sheffield Sheffield UK Leeds Test Objects Ltd. Boroughbridge UK Medical Imaging & Medical Physics Sheffield Teaching Hospitals NHS Foundation Trust Sheffield UK Academic Unit of Radiology Department of Infection Immunity and Cardiovascular Disease University of Sheffield Sheffield UK

Calibration of medical imaging systems that provide quantitative measures relating to complex physiological flows is challenging. Physical test objects available for the purpose either offer a known simple flow far removed from the complexity of pathology (e.g. parabolic flow in a straight pipe) or complex relevant flows in which the details of the flow behaviour are unknown. This paper presents the ring vortex as a candidate for a complex flow phantom, since it is marked by inherently complex flow features that are controllable, predictable, reproducible and stable. These characteristics are demonstrated by a combination of analytical, numerical (CFD) and experimental methods. Together they provide a consistent perspective on ring vortex behaviour and highlight qualities relevant to phantom design. Discussion of the results indicates that a liquid phantom based on the ring vortex may have merit as a complex flow phantom for multimodal imaging. Furthermore, availability of such a flow reference may also serve as a benchmark for quality assurance of simulation methodologies.

关键词： Imaging Phantom Flow Vortex

infection-acquired versus vaccine-acquired immunity in an SIRWS model

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Infectious Disease modelling 2018年第1期3卷 118-135页

作者： Tiffany Leung Patricia T.Campbell Barry D.Hughes Federico Frascoli James M.McCaw School of Mathematics and Statistics University of MelbourneParkvilleVictoria 3010Australia Victorian Infectious Diseases Reference laboratory Epidemiology Unit Peter Doherty Institute for Infection and ImmunityUniversity of Melbourne and Royal Melbourne HospitalParkvilleVictoria 3010Australia infection and immunity Research Theme Murdoch Children's Research InstituteRoyal Children's HospitalParkvilleVictoria 3052Australia Department of Mathematics Faculty of ScienceEngineering and TechnologySwinburne University of TechnologyHawthornVictoria 3122Australia Melbourne School of Population and Global Health University of MelbourneParkvilleVictoria 3010Australia

In some disease systems,the process of waning immunity can be subtle,involving a complex relationship between the duration of immunitydacquired either through natural infection or vaccinationdand subsequent boosting of immunity through asymptomatic *** present and analyse a model of infectious disease transmission where primary and secondary infections are distinguished to examine the interplay between infection and *** we allow the duration of infection-acquired immunity to differ from that of vaccine-acquired immunity to explore the impact on long-term disease patterns and prevalence of infection in the presence of immune *** model demonstrates that vaccination may induce cyclic behaviour,and the ability of vaccinations to reduce primary infections may not lead to decreased *** the boosting of vaccine-acquired immunity delays a primary infection,the driver of transmission largely remains primary *** contrast,if the immune boosting bypasses a primary infection,secondary infections become the main driver of transmission under a sufficiently long duration of *** results show that the epidemiological patterns of an infectious disease may change considerably when the duration of vaccine-acquired immunity differs from that of infection-acquired *** study highlights that for any particular disease and associated vaccine,a detailed understanding of the waning and boosting of immunity and how the duration of protection is influenced by infection prevalence are important as we seek to optimise vaccination strategies.

关键词： Infectious disease modelling Vaccination Waning immunity Immune boosting

IL-17-triggered downregulation of miR-497 results in high HIF-1α expression and consequent IL-1β and IL-6 production by astrocytes in EAE mice

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Cellular & Molecular Immunology 2017年第11期14卷 909-923页

作者： Kai Shan Rongrong Pang Chenhui Zhao Xiaomei Liu Wenxing Gao Jing Zhang Dan Zhao Yingwei Wang Wen Qiu Department of Immunology Nanjing Medical UniversityNanjingJiangsu 211166China Department of Medicine First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of Pathogen Biology and Immunology and laboratory of infection and immunity Xuzhou Medical UniversityXuzhouJiangsu 221004China Basic Medical Science of Basic Medical College Nanjing Medical UniversityNanjingJiangsu211166China

Interleukin 17(IL-17)is increasingly recognized as a key factor that contributes to the pathogenesis of multiple sclerosis(MS)and its experimental mouse autoimmune encephalomyelitis(EAE)***,the roles and regulatory mechanisms of IL-17-induced pro-inflammatory cytokine production in EAE mice remain largely *** this study,the expression of IL-17,hypoxia inducible factor-1α(HIF-1α),IL-1β,IL-6 and microRNA-497(miR-497),as well as their intrinsic associations,was investigated using EAE model mice and cultured astrocytes exposed to IL-17 in *** observed markedly increased production of IL-17,HIF-1α,IL-1βand IL-6 in the brain tissues of EAE mice,while the expression and secretion of HIF-1α,IL-1βand IL-6 were also significantly increased when cultured primary astrocytes from mice were stimulated with ***,the expression of miR-497 was downregulated both in vivo and in *** in vitro experiments revealed that IL-17 induced the production of IL-1βand IL-6 in astrocytes through the upregulation of HIF-1αas a transcriptional factor,indicating that IL-17-mediated downregulation of miR-497 enhanced HIF-1α***,astrocytespecific knockdown of IL-17RA and HIF-1αor astrocyte-specific overexpression of miR-497 by infection with different lentiviral vectors containing an astrocyte-specific promotor markedly decreased IL-1βand IL-6 production in brain tissues and alleviated the pathological changes and score of EAE ***,these findings indicate that decreased miR-497 expression is responsible for IL-17-triggered high HIF-1αexpression and consequent IL-1βand IL-6 production by astrocytes in EAE mice.

关键词： astrocytes experimental autoimmune encephalomyelitis HIF-1α interleukin-17 miR-497

Quality Assuring a Ring Vortex Flow Phantom in Real-Time

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Open Journal of Medical Imaging 2023年第1期13卷 11-29页

作者： Alana S. Matthews Kelvin Simatwo Andrew Narracott Simone Ambrogio Adrian Walker John W. Fenner Department of infection Immunity and Cardiovascular Disease Mathematical Modelling in Medicine Group University of Sheffield Sheffield UK Insigneo Institute for In Silico Medicine University of Sheffield Sheffield UK Department of Electronic and Electrical Engineering University of Sheffield Sheffield UK Medical Physics Department Guy’s and St Thomas’ NHS Foundation Trust London UK Leeds Test Objects Boroughbridge UK

Introduction: The ring vortex phantom is a novel, cost-effective prototype which generates complex and well-characterised reference flows in the form of the ring vortex. Although its reproducibility has been demonstrated, with ring speeds routinely behaving within 10% tolerances at speeds of approximately 10 - 70 cm/s, a form of real-time QA of the device at the time of imaging is needed to confirm correct function on demand in any environment. Methods: The technology described here achieves real-time QA, comprising a linear encoder, laser-photodiode array, and Doppler probe, measuring piston motion, ring speed and intra-ring velocity respectively. This instrumentation does not interfere with imaging system QA, but allows QA to be performed on both the ring vortex and the device in real-time. Results: The encoder reports the reliability of the piston velocity profile, whilst ring speed is measured by laser behaviour. Incorporation of a calibrated Doppler probe offers a consistency check that confirms behaviour of the central axial flow. For purposes of gold-standard measurement, all elements can be related to previous Laser PIV acquisitions with the same device settings. Conclusion: Consequently, ring vortex production within tolerances is confirmed by this instrumentation, delivering accurate QA in real-time. This implementation offers a phantom QA procedure that exceeds anything seen in the literature, providing the technology to enhance quantitative assessment of flow imaging modalities.

关键词： Flow Phantom Ring Vortex Quality Assurance Imaging

Understanding the impact of disease and vaccine mechanisms on the importance of optimal vaccine allocation

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Infectious Disease modelling 2023年第2期8卷 539-550页

作者： Isobel R.Abell James M.McCaw Christopher M.Baker School of Mathematics and Statistics The University of MelbourneMelbourneAustralia Melbourne Centre for Data Science The University of MelbourneMelbourneAustralia Centre for Epidemiology and Biostatistics Melbourne School of Population and Global HealthThe University of MelbourneMelbourneAustralia Peter Doherty Institute for infection and immunity The Royal Melbourne Hospital and the University of MelbourneMelbourneAustralia Centre of Excellence for Biosecurity Risk Analysis The University of MelbourneMelbourneAustralia

Vaccination is an important epidemic intervention ***,it is generally unclear how the outcomes of different vaccine strategies change depending on population characteristics,vaccine mechanisms and allocation *** this paper we develop a conceptual mathematical model to simulate strategies for pre-epidemic *** extend the SEIR model to incorporate a range of vaccine mechanisms and disease *** then compare the outcomes of optimal and suboptimal vaccination strategies for three public health objectives(total infections,total symptomatic infections and total deaths)using numerical *** comparison shows that the difference in outcomes between vaccinating optimally and suboptimally depends on vaccine mechanisms,disease characteristics,and objective *** modelling finds vaccines that impact transmission produce better outcomes as transmission is reduced for all *** vaccines that impact the likelihood of symptomatic disease or dying due to infection,the improvement in outcome as we decrease these variables is dependent on the strategy *** a principled model-based process,this work highlights the importance of designing effective vaccine allocation *** conclude that efficient allocation of resources can be just as crucial to the success of a vaccination strategy as the vaccine effectiveness and/or amount of vaccines available.

关键词： Mathematical modelling Epidemiology

Structures of SARS-CoV-2 spike protein alert noteworthy sites for the potential approaching variants

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Virologica Sinica 2022年第6期37卷 938-941页

作者： Xiaorui Xing Lei Wang Zhen Cui Wangjun Fu Tao Zheng Lili Qin Pingju Ge Aidong Qian Nan Wang Shuai Yuan College of Veterinary Medicine Jilin Agricultural UniversityChangchun130118China College of Animal Science and Technology Jilin Provincial Engineering Research Center of Animal ProbioticsKey Lab of Animal ProductionProduct Quality and SecurityJoint Laboratory of Modern Agricultural Technology International CooperationMinistry of EducationJilin Agricultural UniversityChangchun130118China CAS Key laboratory of infection and immunity National Laboratory of MacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing100101China University of Chinese Academy of Sciences Beijing100101China Acrobiosystems Beijing100101China State Key laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan430071China

Dear Editor,The COVID-19 pandemic, which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has led to millions of lives lost worldwide. The trimeric spike protein(S) decorating the membrane surface of the infectious virion is responsible for the attachment and entry by binding to the receptor angiotensin-converting enzyme 2(ACE2) in the early replication cycle(Zhou P. et al., 2020). Two subunits S1 and S2 are included in the trimeric glycoprotein.

关键词： ACE2 al. acute

Identification of a Novel Universal Potential Epitope on the Cytoplasmic Tail of H7N9 Virus Hemagglutinin

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Virologica Sinica 2019年第3期34卷 334-337页

作者： Xi Liu Li Ding Jing Yuan Jian Liao Lian Duan Wenfei Wang Weiguo Tan Weiye Yu Boping Zhou Xinchun Chen Zheng Yang Department of Infectious Diseases The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhai 51900China lab for Tuberculosis Research Shenzhen Center for Chronic Disease ControlShenzhen 518020China Department of Infectious Diseases The Third People's Hospital of Shenzhen (The Second Affiliated Hospital of Southern University of Science and Technology)Shenzhen 518000China Shenzhen Key laboratory of infection and immunity The Third People's Hospital of Shenzhen (The Second Affiliated Hospital of Southern University of Science and Technology)Shenzhen 518000China Department of Pathogen Biology School of MedicineShenzhen UniversityShenzhen 518000China Longhua Branch of Shenzhen People's Hospital Shenzhen 518000China

Dear Editor,H7N9 is a recently identified subtype of influenza A virus that caused a major outbreak in humans in China in *** to the latest data provided by the Chinese Center for Disease Control and Prevention(http://***/zwgk/yqbb3/***,updated on October 31,2018),the mortality rate of H7N9 infections in China amounts to 39.7%(611/1536).Thus,H7N9 poses a serious public health threat.

关键词： Identification Novel Universal Potential Epitope Cytoplasmic Tail