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Cell signalling pathways underlying induced pluripotent stem cell reprogramming

World Journal of Stem Cells 2014年第5期6卷 620-628页

作者： Kate Hawkins Shona Joy tristan mc kay Molecular Cell Sciences St George’s University of London London SW17 0REUnited Kingdom

Induced pluripotent stem(i PS) cells, somatic cells reprogrammed to the pluripotent state by forced expression of defined factors, represent a uniquely valuable resource for research and regenerative medicine. However, this methodology remains inefficient due to incomplete mechanistic understanding of the reprogramming process. In recent years, various groups have endeavoured to interrogate the cell signalling that governs the reprogramming process, including LIF/STAT3, BMP, PI3 K, FGF2, Wnt, TGFβ and MAPK pathways, with the aim of increasing our understanding and identifying new mechanisms of improving safety, reproducibility and efficiency. This has led to a unified model of reprogramming that consists of 3 stages: initiation, maturation and stabilisation. Initiation of reprogramming occurs in almost all cells that receive the reprogramming transgenes; most commonly Oct4, Sox2, Klf4 and c Myc, and involves a phenotypic mesenchymal-to-epithelial transition. The initiation stage is also characterised by increased proliferation and a metabolic switch from oxidative phosphorylation to glycolysis. The maturation stage is considered the major bottleneck within the process, resulting in very few "stabilisation competent" cells progressing to the final stabilisation phase. To reach this stage in both mouse and human cells, pre-i PS cells must activate endogenous expression of the core circuitry of pluripotency, comprising Oct4, Sox2, and Nanog, and thus reach a state of transgene independence. By the stabilisation stage, i PS cells generally use the same signalling networks that govern pluripotency in embryonic stem cells. These pathways differ between mouse and human cells although recent work has demonstrated that this is context dependent. As i PS cell generation technologies move forward, tools are being developed to interrogate the process in more detail, thus allowing a greater understanding of this intriguing biological phenomenon.

关键词： Pluripotency Reprogramming Induced pluripotent stem Cell signalling Embryonic stem

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A multilocus molecular phylogeny for the avian genus Liocichla(Passeriformes:Leiothrichidae:Liocichla)

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Chinese Birds 2015年第3期6卷 140-152页

作者： Herman L Mays Bailey D mc kay Dieter Thomas Tietze Cheng-Te Yao Lindsey N Miller Kathleen N Moreland Fumin Lei Department of Biological Sciences Marshall University Cincinnati Museum Center American Museum of Natural History Institute of Pharmacy and Molecular Biotechnology Heidelberg University Endemic Species Research Institute Biotechnology Program Loveland High School Institute of Zoology Chinese Academy of Sciences

Background:Historically the babblers have been assigned to the family Timaliidae but several recent studies have attempted to rest the taxonomy of this diverse passerine assemblage on a more firm evolutionary *** result has been a major rearrangement of the group.A well?supported and comprehensive phylogeny for this widespread avian group is an important part of testing evolutionary and biogeographic hypotheses,especially in Asia where the babblers are a key component of many forest ***,the genus Liocichla is poorly represented in these prior studies of babbler ***:We used a multilocus molecular genetic approach to generate a phylogenetic hypothesis for all five cur?rently recognized species in the avian genus *** DNA sequence data was used to construct individ?ual gene trees using maximum likelihood and species trees were estimated from gene trees using Bayesian *** dates were obtained using a molecular clock ***:Molecular data estimate a probable window of time for the origin for the Liocichla from the mid to late Miocene,between 5.55 and 12.87 *** plumage similarities between the insular Taiwan endemic,***,and the continental *** and ***,molecular data suggest that *** is the sister taxon to all continen?tal *** continental Liocichla are comprised of two lineages;a lineage containing *** and *** and a lineage comprised of *** and *** comparatively early divergence of *** within the Liocichla may be illusory due to extinct and therefore unsampled *** and *** are parapatric with a Pleistocene split(0.07–1.88 Ma) occurring between an Eastern Himalayan *** and a Northern Indo?china distributed *** and *** underwent a similar split between the Eastern Himalaya(***) and Central China(***) divided by the Hengduan ***

关键词： Biogeography Himalayas Leiothrichidae Liocichla Phylogenetics Phylogeography Taiwan

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Biomarkers in diabetic nephropathy: Present and future

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World Journal of Diabetes 2014年第6期5卷 763-776页

作者： Gemma Currie Gerard mc kay Christian Delles Institute of Cardiovascular and Medical Sciences University of Glasgow School of Medicine University of Glasgow Glasgow Royal Infirmary

Diabetic nephropathy(DN) is the leading cause of end stage renal disease in the Western world. Microalbuminuria(MA) is the earliest and most commonly used clinical index of DN and is independently associated with cardiovascular risk in diabetic patients. Although MA remains an essential tool for risk stratification and monitoring disease progression in DN, a number of factors have called into question its predictive power. Originally thought to be predictive of future overt DN in 80% of patients, we now know that only around 30% of microalbuminuric patients progress to overt nephropathy after 10 years of follow up. In addition, advanced structural alterations in the glomerular basement membrane may already have occurred by the time MA is clinically *** in recent years suggests that a significant proportion of patients with MA can revert to normoalbuminuria and the concept of nonalbuminuric DN is well-documented, reflecting the fact that patients with diabetes can demonstrate a reduction in glomerular filtration rate without progressing from normo-to MA. There is an unmet clinical need to identify biomarkers with potential for earlier diagnosis and risk stratification in DN and recent developments inthis field will be the focus of this review article.

关键词： Diabetes Nephropathy Microalbuminuria Proteinuria Biomarkers

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新南威尔士新生儿囊性纤维化筛查对其肺部结局的影响

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世界核心医学期刊文摘（儿科学分册） 2006年第A3期2卷 60-61页

作者： mc kay K.O. Waters D.L. Gaskin K.J. 贺文龙 Department of Respiratory Medicine Children's Hospital at Westmead Locked Bag 4001 Westmead NSW 2145 Australia

Objectives: To determine whether early treatment of cystic fibrosis made possible by diagnosis after newborn screening results in improved pulmonary outcomes in adolescence. Study design: Both screening (SG) and non-screening groups (NSG) comprised a cohort of children from Australia previously studied at 1, 5, and 10 years of age. The groups were compared on measures of clinical status obtained during their comprehensive annual review conducted at or near the 15th birthday of the subjects. Results: Data were collected on 48 of 57 original subjects in the NSG (7 had died; 2 were lost to follow-up) and 52 of 60 original subjects in the SG (4 had died; 2 transferred out of the country; 2 were lost to follow-up). Those dying in the SG were significantly older (by 48 months, P < .05) than those in the NSG. No statistically significant differences were found between the groups in nutritional status. However, subjects in the SG displayed statistically better total Shwachman-Kulczycki scores (7.0, P ≤ .05), chest x-ray scores (2.3, P ≤ .05) and lung function (forced expiratory volume in 1 second by 12.3% , P ≤ .01; forced vital capacity by 12.6% , P ≤ .01; and mean airflow by 23.3% , P ≤ .01). Conclusions: The previously observed advantage conferred by cystic fibrosis newborn screening on clinical outcomes in infancy and childhood is still apparent in adolescence.

关键词：囊性纤维化新南威尔士用力呼气量最大肺活量青少年期失访营养状况有显著性差异试验设计临

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High-fidelity multimode fibre-based endoscopy for deep brain in vivo imaging

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Light(Science & Applications) 2018年第1期7卷 193-200页

作者： Sergey Turtaev Ivo T.Leite tristan Altwegg-Boussac Janelle M.P.Pakan Nathalie L.Rochefort Tomáš Čižmár Leibniz Institute of Photonic Technology Albert-Einstein-Straße 9Jena 07745Germany School of Life Sciences University of DundeeNethergateDundee DD14HNUK School of Science and Engineering University of DundeeNethergateDundee DD14HNUK Centre for Discovery Brain Sciences University of EdinburghHugh Robson Building 15George SquareEdinburgh EH89XDUK Center for Behavioral Brain Sciences Institute of Cognitive Neurology and Dementia ResearchGerman Center for Neurodegenerative DiseasesLeipziger Straße 44Haus 64Magdeburg 39120Germany Simons Initiative for the Developing Brain University of EdinburghEdinburgh EH89XDUK Institute of Scientific Instruments of CAS Kralovopolska 147Brno 61264Czech Republic

Progress in neuroscience relies on new techniques for investigating the complex dynamics of neuronal *** ongoing challenge is to achieve minimally invasive and high-resolution observations of neuronal activity in vivo inside deep brain *** introduced methods for holographic control of light propagation in complex media enable the use of a hair-thin multimode optical fibre as an ultranarrow imaging *** to endoscopes based on graded-index lenses or fibre bundles,this new approach offers a footprint reduction exceeding an order of magnitude,combined with a significant enhancement in *** designed a compact and high-speed system for fluorescent imaging at the tip of a fibre,achieving a resolution of 1.18±0.04μm across a 50-μm field of view,yielding 7-kilopixel images at a rate of 3.5 frames/***,we demonstrate in vivo observations of cell bodies and processes of inhibitory neurons within deep layers of the visual cortex and hippocampus of anaesthetised *** study paves the way for modern microscopy to be applied deep inside tissues of living animal models while exerting a minimal impact on their structural and functional properties.

关键词： multimode fibre vivo

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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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