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Multiple checkpoints keep follicular helper T cells under control to prevent autoimmunity

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Cellular & Molecular Immunology 2010年第3期7卷 198-203页

作者： Di Yu Carola G Vinuesa Department of Immunology and Inflammation Garvan Institute of Medical ResearchSydneyNSWAustralia Department of Immunology and Genetics John Curtin School of Medical ResearchCanberraACTAustralia

Follicular helper T(Tfh)cells select mutated B cells in germinal centres,which can then differentiate into long-lived high affinity memory B cells and plasma *** cells are regulated by a unique molecular programme orchestrated by the transcriptional repressor *** transcription factor turns down expression of multiple genes,including transcriptional regulators of other T helper lineages and a vast amount of *** enables Tfh cells to express a suite of chemokine receptors,stimulatory ligands and cytokines that enable migration into B-cell follicles,and provision of effective help to B *** surprisingly,dysregulation of this powerful helper subset can lead to a range of autoantibody-mediated diseases;indeed,aberrant accumulation of Tfh cells has been linked with systemic lupus erythematosus,Sjogren’s disease and autoimmune *** we dissect multiple checkpoints that operate throughout Tfh cell development and maturation to maintain immunological tolerance while mounting robust and long-lasting antibody responses.

关键词： autoimmunity germinal centre Tfh

Cardiovascular computed tomography in cardiovascular disease:An overview of its applications from diagnosis to prediction

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Journal of Geriatric Cardiology 2024年第5期21卷 550-576页

作者： Zhong-Hua SUN Discipline of medical Radiation Science Curtin Medical SchoolCurtin UniversityPerthAustralia curtin Health Innovation research Institute(CHIRI) Curtin UniversityPerth 6012Australia

Cardiovascular computed tomography angiography(CTA)is a widely used imaging modality in the diagnosis of cardiovascular *** in CT imaging technology have further advanced its applications from high diagnostic value to minimising radiation exposure to *** addition to the standard application of assessing vascular lumen changes,CTA-derived applications including 3D printed personalised models,3D visualisations such as virtual endoscopy,virtual reality,augmented reality and mixed reality,as well as CT-derived hemodynamic flow analysis and fractional flow reserve(FFRCT)greatly enhance the diagnostic performance of CTA in cardiovascular *** widespread application of artificial intelligence in medicine also significantly contributes to the clinical value of CTA in cardiovascular *** value of CTA has extended from the initial diagnosis to identification of vulnerable lesions,and prediction of disease extent,hence improving patient care and *** this review article,as an active researcher in cardiovascular imaging for more than 20 years,I will provide an overview of cardiovascular CTA in cardiovascular *** is expected that this review will provide readers with an update of CTA applications,from the initial lumen assessment to recent developments utilising latest novel imaging and visualisation *** will serve as a useful resource for researchers and clinicians to judiciously use the cardiovascular CT in clinical practice.

关键词： diagnosis cardiovascular prediction

Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy

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World Journal of Clinical Cases 2016年第10期4卷 336-343页

作者： Akbar Khan Douglas Andrews Anneke C Blackburn Medicor Cancer Centres Inc. the john curtin school of medical research The Australian National University

Oral dichloroacetate sodium(DCA) has been investigated as a novel metabolic therapy for various cancers since 2007, based on data from Bonnet et al that DCA can trigger apoptosis of human lung, breast and brain cancer cells. Response to therapy in human studies is measured by standard response evaluation criteria for solid tumours definitions, which define "response" by the degree of tumour reduction, or tumour disappearance on imaging. However, Blackburn et al have demonstrated that DCA can also act as a cytostatic agent in vitro and in vivo, without causing apoptosis(programmed cell death). A case is presented in which oral DCA therapy resulted in tumour stabilization of stage 4 colon cancer in a 57 years old female for a period of nearly 4 years, with no serious toxicity. Since the natural history of stage 4 colon cancer consists of steady progression leading to disability and death, this case highlights a novel use of DCA as a cytostatic agent with a potential to maintain long-term stability of advanced-stage cancer.

关键词： Dichloroacetate Cancer Colon Colorectal Cytostatic Stabilization Growth inhibition Intravenous

Harnessing CRISPR-Cas system diversity for gene editing technologies

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The Journal of Biomedical research 2021年第2期35卷 91-106页

作者： Alexander McKay Gaetan Burgio Department of Immunology and Infectious Diseases John Curtin School of Medical ResearchAustralian National UniversityCanberraACT 2601Australia

The discovery and utilization of RNA-guided surveillance complexes,such as CRISPR-Cas9,for sequencespecific DNA or RNA cleavage,has revolutionised the process of gene modification or *** optimise the use of this technology,an exploratory race has ensued to discover or develop new RNA-guided endonucleases with the most flexible sequence targeting requirements,coupled with high cleavage efficacy and *** we review the constraints of existing gene editing and assess the merits of exploiting the diversity of CRISPR-Cas effectors as a methodology for surmounting these limitations.

关键词： CRISPR-Cas systems gene editing biological evolution DNA repair classification DNA transposable elements

Targeting pancreatic ductal adenocarcinoma:New therapeutic options for the ongoing battle

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Hepatobiliary & Pancreatic Diseases International 2022年第1期21卷 4-6页

作者： Pratibha Malhotra Ranjith Palanisamy Marco Falasca Metabolic Signalling Group Curtin Medical SchoolCurtin Health Innovation Research InstituteCurtin UniversityPerthWA6102Australia

Pancreatic ductal adenocarcinoma(PDAC),the most commonly reported form of pancreatic cancer,is a lethal malignancy that con-tributes to the global cancer burden with high morbidity and mor-tality[1].It has a poor 5-year survival mainly because PDAC poses a significant diagnostic challenge,has a high metastatic rate at di-agnosis and is stubbornly resistant to therapy[2].

关键词： adenocarcinoma ductal cancer

Molecular Structure Tailoring of Organic Spacers for High‑Performance Ruddlesden–Popper Perovskite Solar Cells

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Nano-Micro Letters 2025年第2期17卷 314-357页

作者： Pengyun Liu Xuejin Li Tonghui Cai Wei Xing Naitao Yang Hamidreza Arandiyan Zongping Shao Shaobin Wang Shaomin Liu school of Materials Science and Engineering State Key Laboratory of Heavy Oil ProcessingChina University of Petroleum(East China)Qingdao 266580People’s Republic of China school of Chemistry and Chemical Engineering Shandong University of TechnologyZibo 255049People’s Republic of China Centre for Applied Materials and Industrial Chemistry(CAMIC) School of ScienceRMIT UniversityMelbourneVic 3000Australia WA school of Mines:Minerals Energy and Chemical Engineering(WASM‑MECE)Curtin UniversityPerthWA 6102Australia school of Chemical Engineering The University of AdelaideAdelaideSA 5005Australia school of Engineering Great Bay UniversityDongguan 523000People’s Republic of China

Layer-structured Ruddlesden–Popper(RP)perovskites(RPPs)with decent stability have captured the imagination of the photovoltaic research community and bring hope for boosting the development of perovskite solar cell(PSC)***,two-dimensional(2D)or quasi-2D RP PSCs are encountered with some challenges of the large exciton binding energy,blocked charge transport and poor film quality,which restrict their photovoltaic ***,these issues can be readily resolved by rationally designing spacer cations of *** review mainly focuses on how to design the molecular structures of organic spacers and aims to endow RPPs with outstanding photovoltaic *** firstly elucidated the important roles of organic spacers in impacting crystallization kinetics,charge transporting ability and stability of *** we brought three aspects to attention for designing organic ***,we presented the specific molecular structure design strategies for organic spacers of RPPs aiming to improve photovoltaic performance of RP *** proposed strategies in this review will provide new avenues to develop novel organic spacers for RPPs and advance the development of RPP photovoltaic technology for future applications.

关键词： Ruddlesden-Popper perovskites Low-dimensional perovskite solar cells Organic spacers Molecular structure Design strategies

Long-term stabilization of metastatic melanoma with sodium dichloroacetate

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World Journal of Clinical Oncology 2017年第4期8卷 371-377页

作者： Akbar Khan Doug Andrews Jill Shainhouse Anneke C Blackburn Medicor Cancer Centres Inc Insight Naturopathic Clinic the john curtin school of medical research the Australian National University

Sodium dichloroacetate(DCA) has been studied as a metabolic cancer therapy since 2007, based on a publication from Bonnet et al demonstrating that DCA can induce apoptosis(programmed cell death) in human breast, lung and brain cancer cells. Classically, the response of cancer to a medical therapy in human research is measured by Response Evaluation Criterial for Solid Tumours definitions, which define "response" by the degree of tumour reduction, or tumour disappearance on imaging, however disease stabilization is also a beneficial clinical outcome. It has been shown that DCA can function as a cytostatic agent in vitro and in vivo, without causing apoptosis. A case of a 32-year-old male is presented in which DCA therapy, with no concurrent conventional therapy, resulted in regression and stabilization of recurrent metastatic melanoma for over 4 years' duration, with trivial side effects. This case demonstrates that DCA can be used to reduce disease volume and maintain longterm stability in patients with advanced melanoma.

关键词： Dichloroacetate Cancer BRAF Melanoma Cytostatic

Source to sink zircon grain shape:Constraints on selective preservation and significance for Western Australian Proterozoic basin provenance

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Geoscience Frontiers 2018年第2期9卷 415-430页

作者： V.Markwitz C.L.Kirkland school of Earth ■ Environment The University of Western Australia Department of Applied Geology Centre for Exploration Targeting-Curtin NodeJohn de Laeter CentreInstitute of Geoscience Research (TIGeR)Curtin University

The effect of selective preservation during transportation of zircon grains on the detrital age spectrum is difficult to quantify and could potentially lead to systematic bias in provenance analysis. Here we investigate whether the shape of detrital zircon grains holds provenance information and if the grain shape can assist in understanding preservation. We applied multiple linear regression analysis to identify significant shape properties in detrital zircons from Proterozoic metasediments of the Capricorn and Amadeus basins and their Archean and Proterozoic sources in the Yilgarn Craton and the Musgrave Province in Western Australia. Digital images and isotopic data from 819 SIMS U-Pb dated zircons were examined for correlation between grain shape, age, U and Th content. Out of twelve shape descriptors measured, Minor Axis, the width of zircon grains perpendicular to the crystallographic c-axis, consistently shows the most significant correlation with isotopic age. In the studied population Archean grains are narrower than Proterozoic grains: the probability that grains wider than 75 μm are Archean is less than30%.Calculations of the proportions of source material in sedimentary rocks relative to the proportions of source material in the overall catchment area(erosion parameter 'K' calculated based on age spectra)produced values typical for mature river systems, with K = 6 for the Yilgarn-Capricorn and K = 5.5 for the Musgrave-Amadeus source-sink system. For the Yilgarn-Capricorn system, we also calculated 'K' based on Minor Axis, to determine whether grain width can be linked to age populations. Results of the shapebased K of 5.3 suggest a similarity between age-based and shape-based 'K' values, demonstrating that zircon grain width may be a useful discriminator of provenance. Contrary to commonly applied qualitative shape classifications, we found no consistent correlations between shape descriptors of magmatic zircons and the composition of their host rock. Wh

关键词： Zircon grain shape U-Pb geochronology Detrital Whole rock geochemistry Precambrian

CTLA4 protects against maladaptive cytotoxicity during the differentiation of effector and follicular CD4^(+)T cells

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Cellular & Molecular Immunology 2023年第7期20卷 777-793页

作者： Yuwei Hao Bahar Miraghazadeh Rochna Chand Ainsley R.Davies Chelisa Cardinez Kristy Kwong Morgan B.Downes Rebecca A.Sweet Pablo F.Cañete Lloyd J.D’Orsogna David A.Fulcher Sharon Choo Desmond Yip Geoffrey Peters Sonia Yip Matthew J.Witney Maxim Nekrasov Zhi-Ping Feng David C.Tscharke Carola G.Vinuesa Matthew C.Cook Centre for Personalised Immunology John Curtin School of Medical ResearchThe Australian National UniversityCanberraACTAustralia Translational research Unit The Canberra HospitalCanberraACTAustralia Division of Immunology and Infectious Diseases John Curtin School of Medical ResearchThe Australian National UniversityCanberraACTAustralia Department of Immunology Fiona Stanley HospitalPerthWAAustralia Department of Immunology The Royal Children’s HospitalMelbourneVICAustralia Department of medical Oncology The Canberra HospitalCanberraACTAustralia ANU medical school The Australian National UniversityCanberraACTAustralia NHMRC Clinical Trials Unit The University of SydneySydneyNSWAustralia The ACRF Biomolecular Resource Facility John Curtin School of Medical ResearchThe Australian National UniversityCanberraACTAustralia ANU Bioinformatics Consultancy John Curtin School of Medical ResearchThe Australian National UniversityCanberraACTAustralia Francis Crick Institute 1 Midland RdLondon NW11ATUK Cambridge Institute of Therapeutic Immunology and Infectious Disease University of CambridgeCambridgeUnited Kingdom.

As chronic antigenic stimulation from infection and autoimmunity is a feature of primary antibody deficiency(PAD),analysis of affected patients could yield insights into T-cell differentiation and explain how environmental exposures modify clinical phenotypes conferred by single-gene ***57 marks dysfunctional T cells that have differentiated after antigenic ***,while circulating CD57^(+)CD4^(+)T cells are normally rare,we found that they are increased in patients with PAD and markedly increased with CTLA4 haploinsufficiency or *** performed single-cell RNA-seq analysis of matched CD57^(+)CD4^(+)T cells from blood and tonsil *** CD57^(+)CD4^(+)T cells(CD4cyt)exhibited a cytotoxic transcriptome similar to that of CD8^(+)effector cells,could kill B cells,and inhibited B-cell ***4 restrained the formation of *** CD57 also marked an abundant subset of follicular helper T cells,which is consistent with their antigen-driven differentiation,this subset had a preexhaustion transcriptomic signature marked by TCF7,TOX,and ID3 expression and constitutive expression of CTLA4 and did not become cytotoxic even after CTLA4 ***,CD57^(+)CD4^(+)T-cell cytotoxicity and exhaustion phenotypes are compartmentalised between blood and germinal ***4 is a key modifier of CD4^(+)T-cell cytotoxicity,and the pathological CD4cyt phenotype is accentuated by infection.

关键词： CTLA4 Immunodeficiency Cell exhaustion Terminal differentiation Cytotoxic CD4^(+)T cells CD57