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Aneuploidy in pluripotent stem cells and implications for cancerous transformation

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Protein & Cell 2014年第8期5卷 569-579页

作者： Jie Na Duncan Baker Jing Zhang peter w. andrews Ivana Barbaric School of Medicine Tsinghua University Beijing 100084 China Sheffield Diagnostic Genetic Services Sheffield Children's Hospital Sheffield S10 2TH UK Centre for Stem Cell Biology Department of Biomedical Science The University of Sheffield Sheffield S10 2TN UK

Owing to a unique set of attributes, human pluripotent stem cells （hPSCs） have emerged as a promising cell source for regenerative medicine, disease modeling and drug discovery. Assurance of genetic stability over long term maintenance of hPSCs is pivotal in this endeavor, but hPSCs can adapt to life in culture by acquiring non-random genetic changes that render them more robust and easier to grow. In separate studies between 12.5% and 34% of hPSC lines were found to acquire chromosome abnormalities over time, with the incidence increasing with passage number. The predominant genetic changes found in hPSC lines involve changes in chromosome number and structure （particularly of chromosomes 1, 12, 17 and 20）, remi- niscent of the changes observed in cancer cells. In this review, we summarize current knowledge on the causes and consequences of aneuploidy in hPSCs and highlight the potential links with genetic changes observed in human cancers and early embryos. we point to the need for comprehensive characterization of mechanisms underpinning both the acquisition of chromosomal abnormalities and selection pressures, which allow mutations to persist in hPSC cultures. Elucidation of these mechanisms will help to design culture conditions that minimize the appearance of aneuploid hPSCs. Moreover, aneuploidy in hPSCs may provide a unique platform to analyse the driving for- ces behind the genome evolution that may eventually lead to cancerous transformation.

关键词： human pluripotent stem cells (hPSCs),culture adaptation aneuploidy cancer genetic changes

An empirical movement model for sixgill sharks in Puget Sound： Combining observed and unobserved behavior

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Current Zoology 2012年第1期58卷 103-115页

作者： Levin, Phillip S. Horne, peter andrews, Kelly S. williams, Greg Northwest Fisheries Science Center 2725 Montlake Blvd E Seattle WA 98112 USA

Understanding the movement of animals is fundamental to population and community ecology. Historically, it has been difficult to quantify movement patterns of most fishes, but technological advances in acoustic telemetry have increased our abilities to monitor their movement. In this study, we combined small-scale active acoustic tracking with large-scale passive acoustic monitoring to develop an empirical movement model for sixgill sharks in Puget Sound, wA, USA. we began by testing whether a correlated random walk model described the daily movement of sixgills; however, the model failed to capture home-ranging behavior. we added this behavior and used the resultant model （a biased random walk model） to determine whether daily movement patterns are able to explain large-scale seasonal movement. The daily model did not explain the larger-scale pat- terns of movement observed in the passive monitoring data. In order to create the large-scale patterns, sixgills must have per- formed behaviors （large, fast directed movements） that were unobserved during small-scale active tracking. In addition, seasonal shifts in location were not captured by the dally model. we added these ＇unobserved＇ behaviors to the model and were able to capture large-scale seasonal movement of sixgill sharks over 150 days. The development of empirical models of movement al- lows researchers to develop hypotheses and test mechanisms responsible for a species movement behavior and spatial distribution. This knowledge will increase our ability to successfully manage species of concern [Current Zoology 58 （1）： 103-115, 2012].

关键词： Hexanchus griseus Movement Correlated random walk Biased random walk Displacement Movement model

Doctor communication quality and Friends' attitudes influence complementary medicine use in inflammatory bowel disease

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world Journal of Gastroenterology 2015年第12期21卷 3663-3670页

作者： Réme Mountifield Jane M andrews Antonina Mikocka-walus peter Bampton Department of Gastro-enterology and Hepatology Flinders Medical Centre Flinders University of South Australia IBD Service Department of Gastroenterology and Hepatology and School of Medicine University of Adelaide at Royal Adelaide Hospital School of Nursing and Midwifery University of South Australia

AIM: To examine the frequency of regular complementary and alternative therapy(CAM) use in three Australian cohorts of contrasting care setting and geography, and identify independent attitudinal and psychological predictors of CAM use across all cohorts. METHODS: A cross sectional questionnaire was administered to inflammatory bowel disease(IBD) patients in 3 separate cohorts which differed by geographical region and care setting. Demographics and frequency of regular CAM use were assessed, along with attitudes towards IBD medication and psychological parameters such as anxiety, depression, personality traits and quality of life(QOL), and compared across cohorts. Independent attitudinal and psychological predictors of CAM use were determined using binary logistic regression analysis. RESULTS: In 473 respondents(mean age 50.3 years, 60.2% female) regular CAM use was reported by45.4%, and did not vary between cohorts. Only 54.1%of users disclosed CAM use to their doctor. Independent predictors of CAM use which confirm those reported previously were: covert conventional medication dose reduction(P wly identified predictors were CAM use by family or friends(P with patient-doctor communication(P wer depression scores(P w that physician attention to communication and the patient-doctor relationship is important as these factors influence CAM use. Patient reluctance to discuss CAM with physicians may promote greater reliance on social contacts to influence CAM decisions.

关键词： Complementary medicine Alternative therapy Therapy

Outcomes and patients' perspectives of transition from paediatric to adult care in inflammatory bowel disease

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world Journal of Gastroenterology 2016年第8期22卷 2611-2620页

作者： Alice L Bennett David Moore peter A Bampton Robert V Bryant Jane M andrews Department of Gastroenterology Royal Adelaide Hospital North Terrace Adelaide SA 5000 Australia Department of Gastroenterology Flinders Medical Centre Flinders Drive Bedford Park SA 5042 Australia School of Medicine University of Adelaide Adelaide SA 5000 Australia Department of Gastroenterology women's and Children's Hospital Adelaide SA 5006 Australia School of Medicine Flinders University Adelaide SA 5001 Australia

AIM: To describe the disease and psychosocial outcomes of an inflammatory bowel disease (IBD) transition cohort and their ***: Patients with IBD, aged > 18 years, who had moved from paediatric to adult care within 10 years were identified through IBD databases at three tertiary hospitals. Participants were surveyed regarding demographic and disease specific data and their perspectives on the transition process. Survey response data were compared to contemporaneously recorded information in paediatric service case notes. Data were compared to a similar age cohort who had never received paediatric IBD care and therefore who had not undergone a transition ***: There were 81 returned surveys from 46 transition and 35 non-transition patients. No statistically significant differences were found in disease burden, disease outcomes or adult roles and responsibilities between cohorts. Despite a high prevalence of mood disturbance (35%), there was a very low usage (5%) of psychological services in both cohorts. In the transition cohort, knowledge of their transition plan was reported by only 25/46 patients and the majority (54%) felt they were not strongly prepared. A high rate (78%) of discussion about work/study plans was recorded prior to transition, but a near complete absence of discussion regarding sex (8%), and other adult issues was recorded. Both cohorts agreed that their preferred method of future transition practices (of the options offered) was a shared clinic appointment with all key ***: Transition did not appear to adversely affect disease or psychosocial outcomes. Current transition care processes could be optimised, with better psychosocial preparation and agreed transition plans.

关键词： Transition care Crohn’ s disease Ulcerative colitis Chronic illness Inflammatory bowel disease Patient perspectives Disease outcomes

Optical coherence tomography of the living human kidney

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Journal of Innovative Optical Health Sciences 2014年第2期7卷 88-97页

作者： peter M.andrews Hsing-wen wang Jeremiah wierwlle wei Gong Jennifer Verbesey Matthew Cooper Yu Chen Department of Biochemistry Molecular.and Celular Biology Georgetown University MedicalCenter WashingtonDC20007USA Fischell Department of Bioengineering Uriversity of Maryland College ParkMD 20742USA Colege of Photonic and Electric Engineering Fujian Normal University FuzhouChina Medstar Georgetown Transplant Inste Georgetown University Medical Center WashingtonD C 20007USA

Acute tubular necrosis(ATN)induced by ischemia is the most common insult to donor kidneysdestined for *** results from sweling and subsequent damage to cells lining thelkidney *** this study,we demonstrate the capability of optical coherence tomography(OcT)to image the renal microst ructures of living human donor kidneys and potentially providea measure to det ermine the extent of A *** also found that Doppler-based OCT(i.e.,DOCT)reveals renal blood flow dynamics that is another major factor which could relate to post-transplant renal *** OCT/DoCT oberva tions were performed in a noninvasive,sterileand timely manner on intact human kidneys both prior to(er vivo)and following(in vivo)*** results indicate that this imaging model provides transplant surgeons withan objective visualization of the transplant lidneys prior and immediately post transplantation.

关键词： Optical coherence tomography doppler optical coherence tomography acute tubularnecrosis kidney transplantation uriniferous tubules glomerulus renal blood flow

Intravital imaging of adriamycin-induced renal pathology using two-photon microscopy and optical coherence tomography

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Journal of Innovative Optical Health Sciences 2018年第5期11卷 59-68页

作者： Hengchang Guo Hsing-wen wang Qinggong Tang Erik Anderson Reuben Falola Tikina Smith Yi Liu Moshe Levi peter M.andrews Yu Chen Fischell Department of Bioengineering University of Maryland College Park MD 20742USA Department of Biochemistry and Molecular&Cellular Biology Georgetown University Medical Center washington DC 20007 USA Central Animal Resources Facility University of Maryland College ParkMD 20742USA

Adriamycin(doxorubicin),a common cancer chemotherapeutic drug,can be used to induce a model of chronic progressive glomerular disease in *** our studies,we evahuated renal changes in a rat model after Adriamydin injection using two photon microscopy(TPM),optical coherence tomography(OCT)and Doppler OCT(DOCT).Taking advantage of deep penetra-tion and fast scanning speed for three dimensional(3D)label-free imaging,OCT/DOCT system was able to reveal glomerular and tubular pathology noninvasively and in real *** imaging renal pathology following the infusion of fAuorophore-labeled dextrans of different molecular weights,TPM can provide direct views of glomerular and tubular flow dynamics with the onset and progression of renal ***,glomerular permeability and filtration,proximal and distal tubular flow dynamics can be revealed.6-8 weeks after injection of Adriamycin,TPM and OCT/DOCT imaging revealed glomerular sclerosis,compromised flow across the glomerular wall,tubular atrophy,tubular dilation,and variable intra-tubular flow *** results indicate that TPM and OCT/DOCT provide real-time imaging of renal pathology in vivo that has not been previously available using conventional microscopic procedures.

关键词： Chronic kidney disease(CKD) glomeruloscerosis Optical Coherence Tomography(OCT) Tubular Atrophy Two-photon Microscopy(TPM)

Vedolizumab for ulcerative colitis: Real world outcomes from a multicenter observational cohort of Australia and Oxford

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world Journal of Gastroenterology 2020年第30期26卷 4428-4441页

作者： Samba Siva Reddy Pulusu Ashish Srinivasan Krupa Krishnaprasad Daniel Cheng Jakob Begun CharlotteKeung Daniel Van Langenberg Lena Thin Tamara Mogilevski peter De Cruz Graham Radford-Smith Emma Flanagan Sally Bell Soleiman Kashkooli Miles Sparrow Simon Ghaly peter Bampton Elise Sawyer Susan Connor Quart-ul-ain Rizvi Jane M andrews Gillian Mahy Paola Chivers Simon Travis Ian Craig Lawrance Centre for Inflammatory Bowel Diseases St John of God HospitalSubiaco 6008Western AustraliaAustralia Translational Gastroenterology Unit NIHR Oxford Biomedical Research CentreOxford University Hospitals NHS Foundation TrustJohn Radcliffe HospitalOxford OX39DUUnited Kingdom Inflammatory Bowel Disease Research Group Queensland institute of Medical ResearchHerston 4006QueenslandAustralia Department of Gastroenterology Mater HospitalBrisbane 4101QueenslandAustralia Department of Gastroenterology Mater HospitalSouth Brisbane 4101QueenslandAustralia of Gastroenterology Eastern HealthBox Hill 3128VictoriaAustralia Department of Gastroenterology Fiona Stanley HospitalMurdoch 6150Western AustraliaAustralia Department of Gastroenterology Austin HealthHeidelberg 3084VictoriaAustralia Department of Gastroenterology St Vincent’s HospitalFitzroy 3065VictoriaAustralia Department of Gastroenterology Northern HealthEpping 3076VictoriaAustralia Department of Gastroenterology The Alfred HospitalMelbourne 3004VictoriaAustralia Department of Gastroenterology St Vincent’s HospitalDarlinghurst 2010New South WalesAustralia Department of Gastroenterology Flinders Medical CentreBedford Park 5042South AustraliaAustralia Department of Gastroenterology Liverpool HospitalSydney 2170New South WalesAustralia Department of Gastroenterology Royal Adelaide Hospital&University of AdelaideAdelaide 5000South AustraliaAustralia Department of Gastroenterology Townsville HospitalDouglas 4814QueenslandAustralia Institute for Health Research University of Notre DameFremantle 6160Western AustraliaAustralia School of Medicine and Pharmacology University of Western AustraliaCrawley 6009Western AustraliaAustralia

BACKGROUND Vedolizumab(VDZ),a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis(UC)*** To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving *** A retrospective review of Australian and Oxford,United Kingdom data for UC *** response at 3 mo,endoscopic remission at 6 mo and clinical remission at 3,6 and 12 mo were *** regression models and Kaplan Meier curves were performed to assess the time to remission,time to failure and the covariates influencing *** outcomes were *** Three hundred and three UC patients from 14 centres in Australia and United Kingdom,[60%n=182,anti-TNF naïve]were *** clinical response was 79%at 3 mo with more Australian patients achieving clinical response compared to Oxford(83%vs 70%P=0.01).Clinical remission for all patients was 56%,62%and 60%at 3,6 and 12 mo ***-TNF naive patients were more likely to achieve remission than exposed patients at all the time points(3 mo 66%vs 40%Pwere 1.8(95%CI:1.3-2.3)times more likely to achieve remission than anti-TNF exposed(Pwas safe and effective with 60%of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.

关键词： Vedolizumab Ulcerative colitis Outcomes

The Global Stratotype Section and Point （GSSP） for the base of the Holocene Series/Epoch （Quaternary System/Period） in the NGRIP ice core

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Episodes 2008年第2期31卷 264-267页

作者： Mike walker Sigfus Johnsen Sune Olander Rasmussen Jorgen-Peder Steffensen Trevor Popp Philip Gibbard wim Hoek John Lowe John andrews Svante Bjorck Les Cwynar Konrad Hughen peter Kershaw Bernd Kromer Thomas Litt David J. Lowe Takeshi Nakagawa Rewi Newnham Jakob Schwander Department of Archaeology and Anthropology University of Wales Lampeter Wales SA48 7ED UK. Centre for Ice and Climatel The Niels Bohr Institute University of Copenhagen Juliane Maries Vej 30 DK2100 Copenhagen Denmark. Stable Isotope Laboratory Institute of Arctic and Alpine Research University of Colorado Boulder Co 80302 USA. Department of Geography University of Cambridge Downing Place Cambridge CB2 3EN UK. Department-of Physical Geography University of Utrecht Heidelberglaan 2 3508 TC Utrecht The Netherlands. Department of Geography Royal Holloway University of London Egham Surrey TW20 0EX UK. Institute for Arctic and Alpine Research University of Colorado Campus Box 450 Boulder Co 80309 USA. GeoBiosphere Science Centre Quaternary Sciences Lund University S/51veg 12 SE-223 62 Lund Sweden. Department of Biology University of New Brunswick Fredericton New Brunswick Canada E3B 6E1. Department of Marine Chemistry and Geochemistry Woods Hole Oceanographic Institution Woods Hole MA 02543 USA. School of Geography and Environmental Science Monash University Victoria 3800 Australia. Heidelberg Academy of Sciences University of Heidelberg 1NF 229 D-69120 Heidelberg Germany. Institute for Palaeontology University of Bonn Nussallee 8 D-53115 Bonn Germany. Department of Earth and Ocean Sciences University of Waikato Private Bag 3105 Hamilton New Zealand. Department of Geography University of Newcastle Newcastle-upon-Tyne NE 1 7RU UK. School of Geography University of Plymouth Drake Circus Plymouth PIA 8AA UK. Climate and Environmental Physics Physics Institute University of Bern Sidlerstrasse 5 CH-3012 Bern Switzerland.

The Greenland ice core from NorthGRIP （NGRIP） contains a proxy climate record across the Pleistocene-Holocene boundary of unprecedented clarity and resolution. Analysis of an array of physical and chemical parameters within the ice enables the base of the Holocene, as reflected in the first signs of climatic warming at the end of the Younger Dryas/Greenland Stadial 1 cold phase, to be located with a high degree of precision.

关键词：地球全新世第四纪地质时代周期

Generation and preservation of continental crust in the Grenville Orogeny

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Geoscience Frontiers 2015年第3期6卷 357-372页

作者： Christopher J.Spencer peter A.Cawood Chris J.Hawkesworth Anthony R.Prave Nick M.w.Roberts Matthew S.A.Horstwood Martin J.whitehouse EIMF Department of Earth and Environmental Sciences University of St Andrews NERC Isotope Geosciences Laboratory British Geological Survey Swedish Museum of Natural History and Nordic Center for Earth Evolution(NordCEE) Edinburgh Ion Microprobe Facility University of Edinburgh

Detrital zircons from modern sediments display an episodic temporal distribution of U-Pb crystallization ages forming a series of ＇peaks＇ and ＇troughs＇. The peaks are interpreted to represent either periods of enhanced generation of granitic magma perhaps associated with mantle overturn and superplume events, or preferential preservation of continental crust during global collisional orogenesis. The close association of those peaks with the assembly of supercontinents implies a causal relationship between collisional orogenesis and the presence of zircon age peaks. Here these two end-member models （episodic periodicity of increased magmatism versus selective preservation during collisional orogenesis） are assessed using U-Pb, Hf, and 0 analysis of detrital zircons from sedimentary successions deposited during the - 1.3-1.1 Ga accretionary, -1.1-0.9 Ga collisional, and 〈 0.9 Ga extensional collapse phases of the Grenville orogenic cycle in Labrador and Scotland. The pre-collisional, accretionary stage provides a baseline of continental crust present prior to orogenesis and is dominated by Archean and Paleoproterozoic age peaks associated with pre-1300 Ma Laurentian geology. Strata deposited during the Grenville Orogeny display similar Archean and Paleoproterozoic detrital populations along with a series of broad muted peaks from - 1500 to 1100 Ma. However, post-collisional sedimentary successions display a dominant age peak between 1085 and 985 Ma, similar to that observed in modern North American river sediments. Zircons within the post-orogenic sedimentary successions have progressively lower EHf and higher -lSO values from - 1800 to - 1200 Ma whereupon they have higher EHf and -3180 within the dominant 1085-985 Ma age peak. Furthermore, the Lu-Hf isotopic profile of the Grenville-related age peak is consistent with significant assimilation and contamination by older crustal material, The timing of this dominant age peak coincides with the peak of metamorphism and

关键词： Zircon Continental crust Grenville Orogeny Crustal preservation