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physical and toxicological profiles of human IApp amyloids and plaques

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Science Bulletin 2019年第1期64卷 26-35页

作者： Aleksandr Kakinen Yunxiang Sun Ibrahim Javed Ava Faridi Emily H.pilkington pouya Faridi Anthony W.purcell Ruhong Zhou Feng Ding Sijie Lin pu Chun Ke thomas p.davis ARC Centre of Excellence in Convergent Bio-Nano Science and Technology Monash Institute of Pharmaceutical Sciences Monash University Department of physics and Astronomy Clemson University College of Environmental Science and Engineering Shanghai Institute of Pollution Control and Ecological Security Biomedical Multidisciplinary Innovation Research Institute Shanghai East Hospital Tongji University Infection and Immunity program & Department of Biochemistry and Molecular Biology Biomedicine Discovery Institute Monash University IBM thomas J.Watson Research Center Department of Chemistry Columbia University

Although much has been learned about the fibrillization kinetics, structure and toxicity of amyloid proteins, the properties of amyloid fibrils beyond the saturation phase are often perceived as chemically and biologically inert, despite evidence suggesting otherwise. To fill this knowledge gap, we examined the physical and biological characteristics of human islet amyloid polypeptide(IApp) fibrils that were aged up to two months. Not only did aging decrease the toxicity of IApp fibrils, but the fibrils also sequestered fresh IApp and suppressed their toxicity in an embryonic zebrafish model. The mechanical properties of IApp fibrils in different aging stages were probed by atomic force microscopy and sonication, which displayed comparable stiffness but age-dependent fragmentation, followed by self-assembly of such fragments into the largest lamellar amyloid structures reported to date. The dynamic structural and toxicity profiles of amyloid fibrils and plaques suggest that they play active, long-term roles in cell degeneration and may be a therapeutic target for amyloid diseases.

关键词： IApp Amyloid plaque Self assembly Toxicity

Graphene quantum dots rescue protein dysregulation of pancreatic β-cells exposed to human islet amyloid polypeptide

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Nano Research 2019年第11期12卷 2827-2834页

作者： Ava Faridi Yunxiang Sun Monika Mortimer Ritchlynn R.Aranha Aparna Nandakumar Yuhuan Li Ibrahim Javed Aleksandr Kakinen Qingqing Fan Anthony W.purcell thomas p.davis Feng Ding pouya Faridi pu Chun Ke ARC Centre of Excellence in Convergent Bio-Nano Science and Technology Monash Institute of Pharmaceutical SciencesMonash University381 Royal ParadeParkvilleVIC3052Australia Department of physics Ningbo UniversityNingbo315211China Department of physics and Astronomy Clemson UniversityClemsonSC29634USA Institute of Environmental and Health Sciences College of Quality and Safety EngineeringChina Jiliang UniversityHangzhou310018China Infection and Immunity program&Department of Biochemistry and Molecular Biology Biomedicine Discovery InstituteMonash UniversityClaytonVictoria3800Australia Australian Institute for Bioengineering and Nanotechnology The University of QueenslandBrisbaneQld4072Australia

The amyloid aggregation of peptides and proteins is a hallmark of neurological disorders and type 2 *** islet amyloid polypeptide(IApp),co-secreted with insulin by pancreaticβ-cells,plays dual roles in both glycemic control and the pathology of type 2 *** IApp can activate the NLRp3 inflammasome and modulate cellular autophagy,apoptosis and extracellular matrix metabolism,no data is available concerning intracellular protein expression upon exposure to the *** surprisingly,how intracellular protein expression is modulated by nanoparticle inhibitors of protein aggregation remains entirely *** this study,we first examined the changing proteomes ofβTC6,a pancreaticβ-cell line,upon exposure to monomeric,oligomeric and fibrillar IApp,and detailed cellular protein expression rescued by graphene quantum dots(GQDs),an IApp *** found that 29 proteins were significantly dysregulated by the IApp species,while majority of these proteins were nucleotide-binding ***,our liquid chromatography tandem-mass spectrometry,fluorescence quenching,helium ion microscopy,cytotoxicity and discreet molecular dynamics simulations data revealed a remarkable capacity of GQDs in regulating aberrant protein expression through H-bonding and hydrophobic interactions,pointing to nanomedicine as a new frontier against human amyloid diseases.

关键词： islet amyloid polypeptide(IApp) oligomer amyloid protein expression graphene quantum dot

Dual-ratiometric magnetic resonance tunable nanoprobe with acidic-microenvironment-responsive property to enhance the visualization of early tumor pathological changes

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Nano Research 2023年第7期16卷 10034-10046页

作者： Rong Cao Ning Tang Yi Zhu An Chen Yumeng Li Renbin Ge Yuan Li Zhongyi Huang Jiajing Guo Jiali Deng Hongwei Lu Ziwei Lu Helen Forgham thomas pdavis Ruirui Qiao Zhongling Wang Department of Radiology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China School of food science Nanjing Xiaozhuang UniversityNanjing 211171China School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghai 200093China Department of Neurology School of MedicineNew York UniversityNew York 10016USA Department of Biomedical Engineering College of EngineeringShantou UniversityShantou 515063China Department of Radiology The First Affiliated Hospital of Soochow UniversitySuzhou 215006China Australian Institute for Bioengineering and Nanotechnology The University of QueenslandBrisbane QLD 4072Australia

The development of microenvironment-responsive nanoprobes has shown great promise for use in magnetic resonance imaging(MRI),with the advantage of significantly improved specificity and good ***,the clinical application of responsive probes is hampered by a lack of biological sensitivity for early molecular diagnostics and visualizing microenvionment of metabolism reprogramming in tumor ***,we report on a dual-ratiometric magnetic resonance tunable(DMRT)nanoprobe designed by crosslinking different ratios of transferrin chelating gadolinium and superparamagnetic nanoparticles,complexed to a pH responsive biocompatible *** dually activatable nanoprobe enables pH-dependent tumor microenvironment visualization,providing exceptional quantitative pathophysiological information in vitro and in *** used in combination with dual-contrast enhancement triple subtraction imaging technique(DETSI),this smart nanoprobe guarantees the diagnosis of early-stage *** envisage that this novel integrated nanoplatform will provide a new paradigm for the clinical translation of robust DMRT nanoprobes for early disease detection and staging,as well as microenvironment visualization and disease progression monitoring.

关键词： ratiometric nanoprobe dually activatable microenvironment visualization early diagnosis pathological changes

有机砷连接的蛋白/聚合物复合物的制备及自组装行为研究

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有机砷连接的蛋白/聚合物复合物的制备及自组装行为研究

Nanoscale inhibition of polymorphic and ambidextrous lApp amyloid aggregation with small molecules

2015年全国高分子学术论文报告会

作者：刘秋明杜建忠 thomas p.davis 同济大学材料科学与工程学院 ARC Centre of Excellence in Convergent Bio-Nano Science & Technology Faculty of Pharmacy and Pharmaceutical Sciences Monash University (Parkville Campus)

三价有机砷作为一种新型连接剂可以与蛋白上两个位阻相近的硫醇基团结合,从而制备出蛋白/聚合物复合物。本文主要通过两种方法制备温敏型复合物牛血清蛋白/聚异丙基丙烯酰胺（BSA-pNIpAM）:（1）从主链接枝法graft from:先还原BSA上的... 详细信息

三价有机砷作为一种新型连接剂可以与蛋白上两个位阻相近的硫醇基团结合,从而制备出蛋白/聚合物复合物。本文主要通过两种方法制备温敏型复合物牛血清蛋白/聚异丙基丙烯酰胺（BSA-pNIpAM）:（1）从主链接枝法graft from:先还原BSA上的二硫键成巯基,再与带有溴官能团的小分子三价砷结合形成大分子引发剂BSA-Br,通过单电子转移活性自由基聚合（SET-LRp）方法接上温敏型聚合物pNIpAM300从而形成复合物BSA-pNIpAM300;（2）接枝到主链法graft onto:先利用小分子引发剂有机砷引发NIpAM的SET-LRp聚合,再与被还原过的BSA结合形成复合物BSA-pNIpAM80。DLS和TEM结果显示BSA-pNIpAM300的LCST为34.5℃,高于LCST时自组装形成粒径在150 nm左右的囊泡,而BSA-pNIpAM80的LCST为48.5 ℃,高于LCST时自组装形成粒径在50 nm左右的胶束。这种有机砷连接的蛋白/聚合物复合物在小分子药物和大分子蛋白或基因载体上有广阔应用前景。

关键词：牛血清蛋白有机砷复合物温敏自组装

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Nano Research 2018年第7期11卷 3636-3647页

作者： Aleksandr Kakinen Jozef Adamcik Bo Wang Xinwei Ge Raffaele Mezzenga thomas p. davis Feng Ding pu Chun Ke ARC Centre of Excellence in Convergent Bio-Nano Science and Technology Monash Institute of Pharmaceutical Sciences Monash University 381 Royal Parade Parkville VIC 3052 Australia Food & Soft Materials Department of Health Sciences & Technology ETH Zurich Schmelzbergstrasse 9 LFO E23 8092 Zurich Switzerland Department of physics andAstronomy Clemson University Clemson SC29634 USA Department of Chemistry Warwick University Gibbet Hill Coventry CV4 7AL UK

Understanding how small molecules interface with amyloid fibrils at the nanoscale is of importance for developing therapeutic treatments against amyloid-based diseases. Here, we show for the first time that human islet amyloid polypeptides （LApp） in the fibrillar form are polymorphic, ambidextrous, and possess multiple periodicities. Upon interfacing with the small molecule epigallocatechin gallate （EGCG）, IApp aggregation was rendered off-pathway and assumed a form with soft and disordered clusters, while mature IApp fibrils displayed kinks and branching but conserved the twisted fibril morphology. These nanoscale phenomena resulted from competitive interactions between EGCG and the IApp amyloidogenic region, as well as end capping of the fibrils by the small molecule. This information is crucial in delineating IApp toxicity implicated in type 2 diabetes and for developing new inhibitors against amyloidogenesis.

关键词： islet amyloid polypeptides(LApp) fibriUization persistence length small molecule discrete moleculardynamics (DMD)simulations inhibition

Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity

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World Journal of Gastroenterology 2024年第4期30卷 332-345页

作者： Yi-Jie Li Brittney O Baumert Nikos Stratakis Jesse A Goodrich Hao-Tian Wu Jing-Xuan He Yin-Qi Zhao Max T Aung Hong-Xu Wang Sandrah p Eckel Douglas I Walker Damaskini Valvi Michele A La Merrill Justin R Ryder thomas H Inge Todd Jenkins Stephanie Sisley Rohit Kohli Stavra A Xanthakos Andrea A Baccarelli Rob McConnell David V Conti Lida Chatzi Department of population and public Health Sciences Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90032United States Barcelona Institute of Global Health Barcelona Institute of Global HealthBarcelona 08036Spain Department of Environmental Health Sciences Mailman School of Public HealthColumbia UniversityNew YorkNY 10032United States Gangarosa Department of Environmental Health Rollins School of Public HealthEmory UniversityAtlantaGA 30329United States Department of Environmental Medicine and public Health Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States Department of Environmental Toxicology University of CaliforniaDavisCA 95616United States Department of Surgery Lurie Children’s Hospital of ChicagoChicagoIL 60611United States Northwestern University Feinberg School of Medicine Northwestern UniversityChicagoIL 60611United States Division of Biostatistics and Epidemiology Cincinnati Children's Hospital Medical CenterCincinnatiOH 45229United States Department of pediatrics University of Cincinnati College of MedicineCincinnatiOH 45229United States Department of pediatrics Children’s Nutrition Research Center USDA/ARSBaylor College of MedicineHoustonTX 77030United States Department of Gastroenterology Children’s Hospital Los AngelesLos AngelesCA 90027United States Division of Gastroenterology Hepatology and NutritionCincinnati Children's Hospital Medical CenterCincinnatiOH 45229United States

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and *** ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with *** microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains *** analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in *** To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with *** This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery ***-operative core liver biopsies were collected from participants and used to characterize histological features of *** samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq *** examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key *** pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of *** We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with ***,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,***,16 miRNAs were associated with two or more histological features of *** those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and posi

关键词： MicroRNA Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Liver fibrosis Lobular inflammation Ballooning degeneration

Multi-scale interactions in interpersonal coordination

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Journal of Sport and Health Science 2016年第1期5卷 25-34页

作者： Tehran J.davis thomas R.Brooks James A.Dixon Center for the Ecological Study of perception and Action and Department of psychological Sciences University of Connecticu

Background:Interpersonal coordination is an essential aspect of daily life,and crucial to performance in cooperative and competitive team *** empirical research has investigated interpersonal coordination using a wide variety of analytical tools and frameworks,to date very few studies have employed multifractal techniques to study the nature of interpersonal coordination across multiple spatiotemporal *** the present study we address this ***:We investigated the dynamics of a simple dyadic interpersonal coordination task where each participant manually controlled a virtual object in relation to that of his or her *** tested whether the resulting hand-movement time series exhibits multi-scale properties and whether those properties are associated with successful ***:Using the formalism of multifractals,we show that the performance on the coordination task is strongly multi-scale,and that the multi-scale properties appear to arise from interaction-dominant ***,we find that the measure of across-scale interactions,multifractal spectrum width,predicts successful performance at the level of the ***:The results are discussed with respect to the implications of multifractals and interaction-dominance for understanding control in an interpersonal context.

关键词： Component-dominant dynamics Interaction-dominant dynamics Interpersonal coordination Multifractal Time series analysis

A pentaploid-based linkage map of the ancestral octoploid strawberry Fragaria virginiana reveals instances of sporadic hyper-recombination

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Horticulture Research 2020年第1期7卷 1796-1810页

作者： thomas M.davis Yilong Yang Lise L.Mahoney Daniel C.Frailey Department of Agriculture Nutritionand Food SystemsUniversity of New HampshireDurhamNH 03824USA

The first high-resolution genetic linkage map of the ancestral octoploid(2n=8x=56)strawberry species,Fragaria virginiana,was constructed using segregation data obtained from a pentaploid progeny *** novel mapping population of size 178 was generated by crossing highly heterozygous *** hybrid“LB48”as a paternal parent with diploid(2n=2x=14)Fragaria vesca“Hawaii 4”.The LB48 linkage map comprises 6055 markers genotyped on the Axiom®IStraw90 strawberry SNp *** map consists of 28 linkage groups(LGs)organized into seven homoeology groups of four LGs each,and excludes a small 29th LG of undefined *** member of each homoeology group was assignable to an“A”subgenome associated with ancestral diploid Fragaria vesca,while no other subgenomes were *** an intriguing discrepancy within homoeology group VI,synteny comparisons with the previously published Fragaria×ananassa DA×MO linkage map revealed substantial *** initial map construction,examination of crossover distributions revealed that six of the total 5162(=29 chromosomes/individual×178 individuals)chromosomes making up the data set exhibited abnormally high crossover counts,ranging from 15 to 48 crossovers per chromosome,as compared with the overall mean of 0.66 crossovers per *** of these six hyper-recombinant(HypR)chromosomes occurred in a different LG and in a different *** calculated upon exclusion of the six HypR chromosomes,the canonical(i.e.,broadly representative)LB48 map had 1851 loci distributed over a total map length of 1873 cM,while their inclusion increased the number of loci by 130,and the overall map length by 91 *** of these hyper-recombinant chromosomes points to the existence of a sporadically acting mechanism that,if identified and manipulable,could be usefully harnessed for multiple purposes by geneticists and breeders.

关键词： Fragaria straw linkage

Unusual presentations of eosinophilic gastroenteritis:Case series and review of literature

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World Journal of Gastroenterology 2009年第17期15卷 2156-2161页

作者： Rafiq A Sheikh thomas p prindiville R Erick pecha Boris H Ruebner Department of Gastroenterology Kaiser Permanente Medical Center 6600 Bruceville Road SacramentoCA 95823 United States Department of Gastroenterology University of California davis 4150 V Street Sacramento CA95917 United States Department of Gastroenterology Marshall Medical Center 1100 Marshall Way Placerville CA 95667 United States Department of pathology University of California Davis 4150 V Street Sacramento CA 95917 United States

Eosinophilic gastroenteritis (EG) is an uncommon disease characterized by focal or diffuse eosinophilic infiltration of the gastrointestinal tract, and is usually associated with dyspepsia, diarrhea and peripheral eosinophilia. Diffuse gastrointestinal tract and colonic involvement are uncommon. The endoscopic appearance may vary from normal to mucosal nodularity and ulceration. Gastrointestinal obstruction is unusual and is associated with predominantly muscular disease. We present five unusual cases of EG associated with gastric outlet and duodenal obstruction. Two cases presented with acute pancreatitis and one had a history of pancreatitis. Four cases responded well to medical therapy and one had recurrent gastric outlet obstruction that required surgery. Four out of the five cases had endoscopic and histological evidence of esophagitis and two had colitis. Two patients had ascites. These cases reaffirm that EG is a disorder with protean manifestations and may involve the entire gastrointestinal tract. Gastric outlet and/or small bowel obstruction is an important though uncommon presentation of EG. It may also present as esophagitis, gastritis with polypoid lesions, ulcers or erosions, colitis and pancreatitis and may mimic malignancy.

关键词： Gastroenteritis Eosinophilic Gastrointestinal obstruction Eosinophilic esophagitis Eosinophilic colitis Eosinophilic pancreatitis