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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

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Unsupervised ore/waste classification on open-cut mine faces using close-range hyperspectral data

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Geoscience Frontiers 2023年第4期14卷 89-99页

作者： lloyd Windrim Arman Melkumyan Richard j.Murphy Anna Chlingaryan Raymond Leung Rio Tinto Centre for Mine Automation Australian Centre for Field RoboticsThe University of SydneySydney 2006Australia

The remote mapping of minerals and discrimination of ore and waste on surfaces are important tasks for geological applications such as those in *** tasks have become possible using ground-based,close-range hyperspectral sensors which can remotely measure the reflectance properties of the environ-ment with high spatial and spectral ***,autonomous mapping of mineral spectra mea-sured on an open-cut mine face remains a challenging problem due to the subtleness of differences in spectral absorption features between mineral and rock classes as well as variability in the illumination of the *** additional layer of difficulty arises when there is no annotated data available to train a supervised learning algorithm.A pipeline for unsupervised mapping of spectra on a mine face is pro-posed which draws from several recent advances in the hyperspectral machine learning *** proposed pipeline brings together unsupervised and self-supervised algorithms in a unified system to map minerals on a mine face without the need for human-annotated training *** pipeline is eval-uated with a hyperspectral image dataset of an open-cut mine face comprising mineral ore martite and non-mineralised *** combined system is shown to produce a superior map to its constituent algo-rithms,and the consistency of its mapping capability is demonstrated using data acquired at two differ-ent times of day.

关键词： Hyperspectral imaging Mineral mapping Open-cut mine face Machine learning Convolutional neural networks Illumination invariance

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Interleukin-10 suppresses lipid metabolism-mediated intestinal inflammation

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Life Metabolism 2024年第3期3卷 3-5页

作者： Tristram A.j.Ryan Ivan Zanoni division of Immunology and division of Gastroenterology Boston Children’s Hospital and Harvard Medical SchoolBostonMA 02115United States

In a recent paper published in Nature,York et *** that the anti-inflammatory cytokine interleukin(IL)-10 regulates sphingolipid metabolism to limit NF-κB-mediated *** of Il10 in mice,or genetic mutation of IL10 in humans,predisposes to inflammatory bowel disease,which may be overcome by restoring homeostatic sphingolipid metabolism.

关键词： metabolism inflammation al.

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Pangenome analysis of Enterobacteria reveals richness of secondary metabolite gene clusters and their associated gene sets

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Synthetic and Systems Biotechnology 2022年第3期7卷 900-910页

作者： Omkar S.Mohite Colton j.lloyd jonathan M.Monk Tilmann Weber Bernhard O.Palsson The Novo Nordisk Foundation Center for Biosustainability Technical University of DenmarkKongens Lyngby2800Denmark department of Bioengineering University of California San DiegoLa JollaCA92093USA

In silico genome mining provides easy access to secondary metabolite biosynthetic gene clusters(BGCs)encoding the biosynthesis of many bioactive compounds,which are the basis for many important drugs used in human ***,the association between BGCs and other functions encoded in the genomes of producers have remained ***,we present a systems biology workflow that integrates genome mining with a detailed pangenome analysis for detecting genes associated with a particular *** analyzed 3,889 enterobacterial genomes and found 13,266 BGCs,represented by 252 distinct BGC families and 347 additional singletons.A pangenome analysis revealed 88 genes putatively associated with a specific BGC coding for the colon cancer-related colibactin that code for diverse metabolic and regulatory *** presented workflow opens up the possibility to discover novel secondary metabolites,better understand their physiological roles,and provides a guide to identify and analyze BGC associated gene sets.

关键词： Pangenome analysis Workflow Secondary metabolites Colibactin Enterobacteria Secretion systems

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Performance and calibration of quark/gluon-jet taggers using 140 fb^(-1) of pp collisions at √s=13 TeV with the ATLAS detector

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Chinese Physics C 2024年第2期48卷 1-25页

作者： G. Aad B. Abbott K. Abeling N.j. Abicht S.H. Abidi A. Aboulhorma H. Abramowicz H. Abreu Y. Abulaiti B.S. Acharya C. Adam Bourdarios L. Adamczyk S.V. Addepalli M.j. Addison j. Adelman A. Adiguzel T. Adye A.A. Affolder Y. Afik M.N. Agaras j. Agarwala A. Aggarwal C. Agheorghiesei A. Ahmad F. Ahmadov W.S. Ahmed S. Ahuja X. Ai G. Aielli A. Aikot M. Ait Tamlihat B. Aitbenchikh I. Aizenberg M. Akbiyik T.P.A. Åkesson A.V. Akimov d. Akiyama N.N. Akolkar K. Al Khoury G.L. Alberghi j. Albert P. Albicocco G.L. Albouy S. Alderweireldt M. Aleksa I.N. Aleksandrov C. Alexa T. Alexopoulos F. Alfonsi M. Algren M. Alhroob B. Ali H.M.j. Ali S. Ali S.W. Alibocus M. Aliev G. Alimonti W. Alkakhi C. Allaire B.M.M. Allbrooke j.F. Allen C.A. Allendes Flores P.P. Allport A. Aloisio F. Alonso C. Alpigiani M. Alvarez Estevez A. Alvarez Fernandez M. Alves Cardoso M.G. Alviggi M. Aly Y. Amaral Coutinho A. Ambler C. Amelung M. Amerl C.G. Ames d. Amidei S.P. Amor dos Santos K.R. Amos V. Ananiev C. Anastopoulos T. Andeen j.K. Anders S.Y. Andrean A. Andreazza S. Angelidakis A. Angerami A.V. Anisenkov A. Annovi C. Antel M.T. Anthony E. Antipov M. Antonelli F. Anulli M. Aoki T. Aoki j.A. Aparisi Pozo M.A. Aparo L. Aperio Bella C. Appelt A. Apyan N. Aranzabal S.j. Arbiol Val C. Arcangeletti A.T.H. Arce E. Arena j-F. Arguin S. Argyropoulos j.-H. Arling O. Arnaez H. Arnold G. Artoni H. Asada K. Asai S. Asai N.A. Asbah j. Assahsah K. Assamagan R. Astalos S. Atashi R.j. Atkin M. Atkinson H. Atmani P.A. Atmasiddha K. Augsten S. Auricchio A.d. Auriol V.A. Austrup G. Avolio K. Axiotis G. Azuelos d. Babal H. Bachacou K. Bachas A. Bachiu F. Backman A. Badea P. Bagnaia M. Bahmani A.j. Bailey V.R. Bailey j.T. Baines L. Baines O.K. Baker E. Bakos d. Bakshi Gupta V. Balakrishnan R. Balasubramanian E.M. Baldin P. Balek E. Ballabene F. Balli L.M. Baltes W.K. Balunas j. Balz E. Banas M. Bandieramonte A. Bandyopadhyay S. Bansal L. Barak M. Barakat E.L. Barberio d. Barberis M. Barbero M.Z. Barel K.N. Barends T. Barillari M-S. Barisits T. Barklow P. Baron d.A. Baron Mo The ATLAS Collaboration

The identification of jets originating from quarks and gluons,often referred to as quark/gluon tagging,plays an important role in various analyses performed at the Large Hadron Collider,as Standard Model measurements and searches for new particles decaying to quarks often rely on suppressing a large gluon-induced *** paper describes the measurement of the efficiencies of quark/gluon taggers developed within the ATLAS Collaboration,using √s=13 TeV proton–proton collision data with an integrated luminosity of 140 fb^(-1) collected by the ATLAS *** taggers with high performances in rejecting jets from gluon over jets from quarks are studied:one tagger is based on requirements on the number of inner-detector tracks associated with the jet,and the other combines several jet substructure observables using a boosted decision tree.A method is established to determine the quark/gluon fraction in data,by using quark/gluon-enriched subsamples defined by the jet *** in tagging efficiency between data and simulation are provided for jets with transverse momentum between 500 GeV and 2 TeV and for multiple tagger working points.

关键词： ATLAS jET QUARK GLUON TAGGING

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Mass Spectrometric Analyses Reveal a Central Role for Ubiquitylation in Remodeling the Arabidopsis Proteome during Photomorphogenesis

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Molecular Plant 2017年第6期10卷 846-865页

作者： Victor Aguilar-Hernandez do-Young Kim Robert j. Stankey Mark Scalf lloyd M. Smith Richard d. Vierstra department of Biology Washington University in St. Louis Campus Box 1137 One Brookings Drive St. Louis MO 63130 USA department of Genetics 425-G Henry Mall department of Chemistry 1101 University Avenue University of Wisconsin-Madison Madison WI 53706 USA Advanced Bio Convergence Center Pohang Technopark Gyeong-Buk South Korea 37668

The switch from skotomorphogenesis to photomorphogenesis is a key developmental transition in the life of seed plants. While much of the underpinning proteome remodeling is driven by light-induced changes in gene expression, the proteolytic removal of specific proteins by the ubiquitin-26S proteasome system is also likely paramount. Through mass spectrometric analysis of ubiquitylated proteins affinity-purified from etiolated Arabidopsis seedlings before and after red-light irradiation, we identified a number of influential proteins whose ubiquitylation status is modified during this switch. We observed a substantial enrichment for proteins involved in auxin, abscisic acid, ethylene, and brassinosteroid signaling, peroxisome function, disease resistance, protein phosphorylation and light perception, including the phytochrome （Phy） A and phototropin photoreceptors. Soon after red-light treatment, PhyA becomes the dominant ubiquitylated species, with ubiquitin attachment sites mapped to six lysines. A PhyA mutant protected from ubiquitin addition at these sites is substantially more stable in planta upon photoconversion to Pfr and is hyperactive in driving photomorphogenesis. However, light still stimulates ubiquitylation and degradation of this mutant, implying that other attachment sites and/or proteolytic pathways exist. Collectively, we expand the catalog of ubiquitylation targets in Arabidopsis and show that this post- translational modification is central to the rewiring of plants for photoautotrophic growth.

关键词： Arabidopsis ubiquitin mass spectrometry photomorphogenesis phytochrome degradation

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Tracking the Cretaceous transcontinental Ceduna River through Australia:The hafnium isotope record of detrital zircons from offshore southern Australia

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Geoscience Frontiers 2016年第2期7卷 237-244页

作者： jarred lloyd Alan S.Collins justin L.Payne Stijn Glorie Simon Holford Anthony j.Reid Centre for Tectonics Resources and Exploration(TRaX)Department of Earth SciencesThe University of Adelaide Centre for Tectonics Resources and Exploration(TRaX)School of Built and Natural EnvironmentsThe University of South Australia Centre for Tectonics Resources and Exploration(TRaX)Australian School of PetroleumThe University of Adelaide Geological Survey of South Australia Department of State DevelopmentGovernment of South Australia

The middle-upper Cretaceous Ceduna River system traversed continental Australia from the NE coast to the centre of the southern coast. At its mouth, it formed a vast delta system that is similar in scale to the Niger delta of West Africa. The delta system is composed of two main lobes that represent different phases of delta construction. A recent hypothesis has challenged the traditional idea that both lobes of the delta were derived from a transcontinental river system by suggesting that the upper lobe （Santonian -Maastrichtian） is instead derived from a restricted catchment within southern Australia. Hf isotopic data presented here fingerprint the original source of the upper delta lobe zircons to NE Australia, with data comparing well with similar U-Pb and Lu-Hf isotopic data from the Lachlan Orogen, the New England Orogen, the eastern Musgraves Province and the northern Flinders Ranges. These data do not preclude a model where the lobe is derived from recycled Eromanga Basin sediments during a phase of late Cretaceous inland Australian uplift, but when coupled with reconnaissance low-temperature thermochronometry from the region of the Ceduna River course indicating widespread Triassic-jurassic exhumation, and comparisons with detrital zircon data from the Winton Formation upstream of any proposed uplift, we suggest that both lobes of the Ceduna delta are likely to be derived from a transcontinental Ceduna River.

关键词： detrital zircon Hf U-Pb Ceduna sub-basin Bight basin Australia

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High yield reproducible rat model recapitulating human Barrett's carcinogenesis

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World journal of Gastroenterology 2017年第33期23卷 6077-6087页

作者： daisuke Matsui Ashten N Omstead juliann E Kosovec Yoshihiro Komatsu Emily j lloyd Hailey Raphael Ronan j Kelly Ali H Zaidi Blair A jobe Esophageal and Lung Institute Allegheny Health Network department of Gastroenterological Surgery Kanazawa University Hospital department of Oncology Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins Hospital

AIM To efficiently replicate the biology and pathogenesis of human esophageal adenocarcinoma(EAC) using the modified Levrat model of end-to-side esophagojejunostomy. METHOdS End-to-side esophagojejunostomy was performed on rats to induce gastroduodenoesophageal reflux to develop EAC. Animals were randomly selected and serially euthanized at 10(n = 6),17(n = 8),24(n = 9),31(n = 6),38(n = 6),and 40(n = 6) wk postoperatively. The esophagi were harvested for downstream histopathology and gene expression. Histological evaluation wascompleted to determine respective rates of carcinogenic development. Quantitative reverse transcriptionpolymerase chain reaction was performed to determine gene expression levels of MUC2,CK19,and CK20,and results were compared to determine significant differences throughout disease progression *** The overall study mortality was 15%. Causes of mortality included anastomotic leak,gastrointestinal hemorrhage,stomach ulcer perforation,respiratory infection secondary to aspiration,and obstruction due to tumor or late anastomotic stricture. 10 wk following surgery,100% of animals presented with esophagitis. Barrett's esophagus(BE) was first observed at 10 wk,and was present in 100% of animals by 17 wk. dysplasia was confirmed in 87.5% of animals at 17 wk,and increased to 100% by 31 wk. EAC was first observed in 44.4% of animals at 24 wk and increased to 100% by 40 wk. In addition,two animals at 38-40 wk post-surgery had confirmed macro-metastases in the lung/liver and small intestine,respectively. MUC2 gene expression was progressively down-regulated from BE to dysplasia to EAC. Both CK19 and CK20 gene expression significantly increased in a stepwise manner from esophagitis to EAC. CONCLUSION Esophagojejunostomy was successfully replicated in rats with low mortality and a high tumor burden,which may facilitate broader adoption to study EAC development,progression,and therapeutics.

关键词： Esophageal adenocarcinoma gastroeso phageal reflux disease Levrat Esophagojejunostomy Experimental rat model Mucin genes Cytokeratins

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Scientific evidence is just the starting point: A generalizable process for developing sports injury prevention interventions

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journal of Sport and Health Science 2016年第3期5卷 334-341页

作者： Alex donaldson david G.lloyd Belinda j.Gabbe jill Cook Warren Young Peta White Caroline F.Finch Australian Centre for Research into Injury in Sport and its Prevention (ACRISP) Federation University Australia Centre for Musculoskeletal Research Griffith Health Institute Griffith University department of Epidemiology and Preventive Medicine Monash University La Trobe Sport and Exercise Medicine Research Centre La Trobe University School of Health Sciences Federation University Australia

Background: The 2 most cited sports injury prevention research frameworks incorporate intervention development, yet little guidance is available in the sports science literature on how to undertake this complex process. This paper presents a generalizable process for developing implementable sports injury prevention interventions, including a case study applying the process to develop a lower limb injury prevention exercise training program(Footy First) for community Australian ***: The intervention development process is underpinned by 2 complementary premises:(1) that evidence-based practice integrates the best available scientific evidence with practitioner expertise and end user values and(2) that research evidence alone is insufficient to develop implementable ***: The generalizable 6-step intervention development process involves(1) compiling research evidence, clinical experience, and knowledge of the implementation context;(2) consulting with experts;(3) engaging with end users;(4) testing the intervention;(5) using theory; and(6)obtaining feedback from early implementers. Following each step, intervention content and presentation should be revised to ensure that the final intervention includes evidence-informed content that is likely to be adopted, properly implemented, and sustained over time by the targeted intervention deliverers. For Footy First, this process involved establishing a multidisciplinary intervention development group, conducting 2targeted literature reviews, undertaking an online expert consensus process, conducting focus groups with program end users, testing the program multiple times in different contexts, and obtaining feedback from early implementers of the ***: This systematic yet pragmatic and iterative intervention development process is potentially applicable to any injury prevention topic across all sports settings and levels. It will guide researchers wishing to undertake interventio

关键词： Australian football Implementation Intervention development Lower limb injuries Research-to-practice Sports injury prevention Translation

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Protein Precipitation to Remove Carbohydrates that Interfere in Protein-Bound Tryptophan Quantification in Soybean Seeds

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journal of Analysis and Testing 2020年第3期4卷 238-247页

作者： Zhentian Lei Santosh Kumar Saurav j.Sarma Ritesh Kumar Barbara W.Sumner Minviluz G.Stacey lloyd W.Sumner University of Missouri Metabolomics Center ColumbiaMO 65211USA division of Biochemistry University of MissouriColumbiaMO 65211USA division of Plant Sciences University of MissouriColumbiaMO 65211USA

Tryptophan is one of the nine essential amino acids in humans that can only be obtained through diets and *** is a precursor to many biological processes,such as serotonin,melatonin,kynurenin,and niacin(nicotinamide)vitamin *** content of tryptophan in foods,such as soybean is an important indicator of nutritional ***,accurate quantification of tryptophan in soybean is crucial to soybean nutritional *** of soybean protein-bound amino acids first involves acid hydrolysis of total protein to liberate amino ***,tryptophan quantification following acid hydrolysis is difficult or impossible due to its reactions with soybean ***,removal of carbohydrates from soy proteins prior to acid hydrolysis is *** this study,we compared four common protein precipitation methods(i.e.,methanol,acetonitrile,acetone,and trichloroacetic acid(TCA)protein precipitation methods)to determine the best method to separate soy proteins from carbohydrates,and concluded that acetone provided the highest recovery of soy *** content in the precipitated proteins was determined after acid hydrolysis of the proteins using liquid chromatography-tandem mass spectrometry multiple reaction monitoring(LC-MS/MS-MRM).No significant difference in the tryptophan content was found among proteins precipitated with methanol,acetonitrile,and TCA,suggesting that these precipitated proteins have similar compositions.A slightly lower,but statistically significant tryptophan content was found in the acetonitrile-precipitated proteins,suggesting that these proteins contain slightly higher glycosylated proteins.

关键词： Tryptophan Acid hydrolysis LC-MS/MS MRM Soybean seeds Protein precipitation

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