scispace - formally typeset
Search or ask a question

Showing papers by "University College London published in 2009"


Journal ArticleDOI
TL;DR: The Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines target the reliability of results to help ensure the integrity of the scientific literature, promote consistency between laboratories, and increase experimental transparency.
Abstract: Background: Currently, a lack of consensus exists on how best to perform and interpret quantitative real-time PCR (qPCR) experiments. The problem is exacerbated by a lack of sufficient experimental detail in many publications, which impedes a reader’s ability to evaluate critically the quality of the results presented or to repeat the experiments. Content: The Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines target the reliability of results to help ensure the integrity of the scientific literature, promote consistency between laboratories, and increase experimental transparency. MIQE is a set of guidelines that describe the minimum information necessary for evaluating qPCR experiments. Included is a checklist to accompany the initial submission of a manuscript to the publisher. By providing all relevant experimental conditions and assay characteristics, reviewers can assess the validity of the protocols used. Full disclosure of all reagents, sequences, and analysis methods is necessary to enable other investigators to reproduce results. MIQE details should be published either in abbreviated form or as an online supplement. Summary: Following these guidelines will encourage better experimental practice, allowing more reliable and unequivocal interpretation of qPCR results.

12,469 citations


Journal ArticleDOI
TL;DR: A series of improvements to the spectroscopic reductions are described, including better flat fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities.
Abstract: This paper describes the Seventh Data Release of the Sloan Digital Sky Survey (SDSS), marking the completion of the original goals of the SDSS and the end of the phase known as SDSS-II. It includes 11,663 deg^2 of imaging data, with most of the ~2000 deg^2 increment over the previous data release lying in regions of low Galactic latitude. The catalog contains five-band photometry for 357 million distinct objects. The survey also includes repeat photometry on a 120° long, 2°.5 wide stripe along the celestial equator in the Southern Galactic Cap, with some regions covered by as many as 90 individual imaging runs. We include a co-addition of the best of these data, going roughly 2 mag fainter than the main survey over 250 deg^2. The survey has completed spectroscopy over 9380 deg^2; the spectroscopy is now complete over a large contiguous area of the Northern Galactic Cap, closing the gap that was present in previous data releases. There are over 1.6 million spectra in total, including 930,000 galaxies, 120,000 quasars, and 460,000 stars. The data release includes improved stellar photometry at low Galactic latitude. The astrometry has all been recalibrated with the second version of the USNO CCD Astrograph Catalog, reducing the rms statistical errors at the bright end to 45 milliarcseconds per coordinate. We further quantify a systematic error in bright galaxy photometry due to poor sky determination; this problem is less severe than previously reported for the majority of galaxies. Finally, we describe a series of improvements to the spectroscopic reductions, including better flat fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities.

5,665 citations


Journal ArticleDOI
Shaun Purcell1, Shaun Purcell2, Naomi R. Wray3, Jennifer Stone2, Jennifer Stone1, Peter M. Visscher, Michael Conlon O'Donovan4, Patrick F. Sullivan5, Pamela Sklar1, Pamela Sklar2, Douglas M. Ruderfer, Andrew McQuillin, Derek W. Morris6, Colm O'Dushlaine6, Aiden Corvin6, Peter Holmans4, Stuart MacGregor3, Hugh Gurling, Douglas Blackwood7, Nicholas John Craddock5, Michael Gill6, Christina M. Hultman8, Christina M. Hultman9, George Kirov4, Paul Lichtenstein9, Walter J. Muir7, Michael John Owen4, Carlos N. Pato10, Edward M. Scolnick2, Edward M. Scolnick1, David St Clair, Nigel Williams4, Lyudmila Georgieva4, Ivan Nikolov4, Nadine Norton4, Hywel Williams4, Draga Toncheva, Vihra Milanova, Emma Flordal Thelander9, Patrick Sullivan11, Elaine Kenny6, Emma M. Quinn6, Khalid Choudhury12, Susmita Datta12, Jonathan Pimm12, Srinivasa Thirumalai13, Vinay Puri12, Robert Krasucki12, Jacob Lawrence12, Digby Quested14, Nicholas Bass12, Caroline Crombie15, Gillian Fraser15, Soh Leh Kuan, Nicholas Walker, Kevin A. McGhee7, Ben S. Pickard16, P. Malloy7, Alan W Maclean7, Margaret Van Beck7, Michele T. Pato10, Helena Medeiros10, Frank A. Middleton17, Célia Barreto Carvalho10, Christopher P. Morley17, Ayman H. Fanous, David V. Conti10, James A. Knowles10, Carlos Ferreira, António Macedo18, M. Helena Azevedo18, Andrew Kirby1, Andrew Kirby2, Manuel A. R. Ferreira1, Manuel A. R. Ferreira2, Mark J. Daly2, Mark J. Daly1, Kimberly Chambert2, Finny G Kuruvilla2, Stacey Gabriel2, Kristin G. Ardlie2, Jennifer L. Moran2 
06 Aug 2009-Nature
TL;DR: The extent to which common genetic variation underlies the risk of schizophrenia is shown, using two analytic approaches, and the major histocompatibility complex is implicate, which is shown to involve thousands of common alleles of very small effect.
Abstract: Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%(1,2). We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.

4,573 citations


Journal ArticleDOI
TL;DR: In this paper, the authors presented an updated leading-order, next-to-leading order and next-next-ordering order parton distribution function (MSTW 2008) determined from global analysis of hard-scattering data within the standard framework of leading-twist fixed-order collinear factorisation in the $\overline{\mathrm{MS}}$¯¯$¯¯¯¯¯
Abstract: We present updated leading-order, next-to-leading order and next-to-next-to-leading order parton distribution functions (“MSTW 2008”) determined from global analysis of hard-scattering data within the standard framework of leading-twist fixed-order collinear factorisation in the $\overline{\mathrm{MS}}$ scheme. These parton distributions supersede the previously available “MRST” sets and should be used for the first LHC data taking and for the associated theoretical calculations. New data sets fitted include CCFR/NuTeV dimuon cross sections, which constrain the strange-quark and -antiquark distributions, and Tevatron Run II data on inclusive jet production, the lepton charge asymmetry from W decays and the Z rapidity distribution. Uncertainties are propagated from the experimental errors on the fitted data points using a new dynamic procedure for each eigenvector of the covariance matrix. We discuss the major changes compared to previous MRST fits, briefly compare to parton distributions obtained by other fitting groups, and give predictions for the W and Z total cross sections at the Tevatron and LHC.

3,546 citations


Journal ArticleDOI
Denise Harold1, Richard Abraham2, Paul Hollingworth2, Rebecca Sims2, Amy Gerrish2, Marian L. Hamshere3, Jaspreet Singh Pahwa2, Valentina Moskvina2, Kimberley Dowzell2, Amy L. Williams2, Nicola L. Jones2, Charlene Thomas2, Alexandra Stretton2, Angharad R. Morgan2, Simon Lovestone4, John Powell5, Petroula Proitsi5, Michelle K. Lupton5, Carol Brayne6, David C. Rubinsztein7, Michael Gill6, Brian A. Lawlor6, Aoibhinn Lynch6, Kevin Morgan8, Kristelle Brown8, Peter Passmore9, David Craig9, Bernadette McGuinness9, Stephen Todd9, Clive Holmes10, David M. A. Mann11, A. David Smith12, Seth Love3, Patrick G. Kehoe3, John Hardy, Simon Mead13, Nick C. Fox13, Martin N. Rossor13, John Collinge13, Wolfgang Maier14, Frank Jessen14, Britta Schürmann14, Hendrik van den Bussche15, Isabella Heuser16, Johannes Kornhuber17, Jens Wiltfang18, Martin Dichgans19, Lutz Frölich20, Harald Hampel21, Harald Hampel19, Michael Hüll22, Dan Rujescu19, Alison Goate23, John S. K. Kauwe24, Carlos Cruchaga23, Petra Nowotny23, John C. Morris23, Kevin Mayo23, Kristel Sleegers25, Karolien Bettens25, Sebastiaan Engelborghs25, Peter Paul De Deyn25, Christine Van Broeckhoven25, Gill Livingston26, Nicholas Bass26, Hugh Gurling26, Andrew McQuillin26, Rhian Gwilliam27, Panagiotis Deloukas27, Ammar Al-Chalabi28, Christopher Shaw28, Magda Tsolaki29, Andrew B. Singleton30, Rita Guerreiro30, Thomas W. Mühleisen14, Markus M. Nöthen14, Susanne Moebus18, Karl-Heinz Jöckel18, Norman Klopp, H-Erich Wichmann19, Minerva M. Carrasquillo31, V. Shane Pankratz31, Steven G. Younkin31, Peter Holmans2, Michael Conlon O'Donovan2, Michael John Owen2, Julie Williams2 
TL;DR: A two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals, the most powerful AD GWAS to date, produced compelling evidence for association with Alzheimer's Disease in the combined dataset.
Abstract: We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 10-157) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.4 10-9) and 5' to the PICALM gene (rs3851179, P = 1.9 10-8). These associations were replicated in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with Alzheimer's disease in the combined dataset (rs11136000, P = 8.5 10-10, odds ratio = 0.86; rs3851179, P = 1.3 10-9, odds ratio = 0.86).

2,956 citations


Journal ArticleDOI
TL;DR: A comprehensive systematic review and meta-analysis of cohort studies in which women who had developed type 2 diabetes after gestational diabetes were followed up between Jan 1, 1960, and Jan 31, 2009 to assess the strength of association between these conditions and the effect of factors that might modify the risk.

2,640 citations


Book
01 Jan 2009
TL;DR: A survey of previous comparisons and theoretical work descriptions of methods dataset descriptions criteria for comparison and methodology (including validation) empirical results machine learning on machine learning can be found in this article, where the authors also discuss their own work.
Abstract: Survey of previous comparisons and theoretical work descriptions of methods dataset descriptions criteria for comparison and methodology (including validation) empirical results machine learning on machine learning.

2,325 citations


Journal ArticleDOI
Lorenzo Galluzzi1, Lorenzo Galluzzi2, Lorenzo Galluzzi3, Stuart A. Aaronson4, John M. Abrams5, Emad S. Alnemri6, David W. Andrews7, Eric H. Baehrecke8, Nicolas G. Bazan9, Mikhail V. Blagosklonny10, Klas Blomgren11, Klas Blomgren12, Christoph Borner13, Dale E. Bredesen14, Dale E. Bredesen15, Catherine Brenner16, Maria Castedo1, Maria Castedo3, Maria Castedo2, John A. Cidlowski17, Aaron Ciechanover18, Gerald M. Cohen19, V De Laurenzi20, R De Maria21, Mohanish Deshmukh22, Brian David Dynlacht23, Wafik S. El-Deiry24, Richard A. Flavell25, Richard A. Flavell26, Simone Fulda27, Carmen Garrido28, Carmen Garrido2, Pierre Golstein29, Pierre Golstein2, Pierre Golstein16, Marie-Lise Gougeon30, Douglas R. Green, Hinrich Gronemeyer16, Hinrich Gronemeyer2, Hinrich Gronemeyer31, György Hajnóczky6, J. M. Hardwick32, Michael O. Hengartner33, Hidenori Ichijo34, Marja Jäättelä, Oliver Kepp1, Oliver Kepp2, Oliver Kepp3, Adi Kimchi35, Daniel J. Klionsky36, Richard A. Knight37, Sally Kornbluth38, Sharad Kumar, Beth Levine5, Beth Levine26, Stuart A. Lipton, Enrico Lugli17, Frank Madeo39, Walter Malorni21, Jean-Christophe Marine40, Seamus J. Martin41, Jan Paul Medema42, Patrick Mehlen16, Patrick Mehlen43, Gerry Melino19, Gerry Melino44, Ute M. Moll45, Ute M. Moll46, Eugenia Morselli1, Eugenia Morselli2, Eugenia Morselli3, Shigekazu Nagata47, Donald W. Nicholson48, Pierluigi Nicotera19, Gabriel Núñez36, Moshe Oren35, Josef M. Penninger49, Shazib Pervaiz50, Marcus E. Peter51, Mauro Piacentini44, Jochen H. M. Prehn52, Hamsa Puthalakath53, Gabriel A. Rabinovich54, Rosario Rizzuto55, Cecília M. P. Rodrigues56, David C. Rubinsztein57, Thomas Rudel58, Luca Scorrano59, Hans-Uwe Simon60, Hermann Steller26, Hermann Steller61, J. Tschopp62, Yoshihide Tsujimoto63, Peter Vandenabeele64, Ilio Vitale1, Ilio Vitale3, Ilio Vitale2, Karen H. Vousden65, Richard J. Youle17, Junying Yuan66, Boris Zhivotovsky67, Guido Kroemer3, Guido Kroemer1, Guido Kroemer2 
Institut Gustave Roussy1, French Institute of Health and Medical Research2, University of Paris-Sud3, Icahn School of Medicine at Mount Sinai4, University of Texas Southwestern Medical Center5, Thomas Jefferson University6, McMaster University7, University of Massachusetts Medical School8, LSU Health Sciences Center New Orleans9, Roswell Park Cancer Institute10, University of Gothenburg11, Boston Children's Hospital12, University of Freiburg13, Buck Institute for Research on Aging14, University of California, San Francisco15, Centre national de la recherche scientifique16, National Institutes of Health17, Technion – Israel Institute of Technology18, University of Leicester19, University of Chieti-Pescara20, Istituto Superiore di Sanità21, University of North Carolina at Chapel Hill22, New York University23, University of Pennsylvania24, Yale University25, Howard Hughes Medical Institute26, University of Ulm27, University of Burgundy28, Aix-Marseille University29, Pasteur Institute30, University of Strasbourg31, Johns Hopkins University32, University of Zurich33, University of Tokyo34, Weizmann Institute of Science35, University of Michigan36, University College London37, Duke University38, University of Graz39, Ghent University40, Trinity College, Dublin41, University of Amsterdam42, University of Lyon43, University of Rome Tor Vergata44, University of Göttingen45, Stony Brook University46, Kyoto University47, Merck & Co.48, Austrian Academy of Sciences49, National University of Singapore50, University of Chicago51, Royal College of Surgeons in Ireland52, La Trobe University53, University of Buenos Aires54, University of Padua55, University of Lisbon56, University of Cambridge57, University of Würzburg58, University of Geneva59, University of Bern60, Rockefeller University61, University of Lausanne62, Osaka University63, University of California, San Diego64, University of Glasgow65, Harvard University66, Karolinska Institutet67
TL;DR: A nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls is provided and the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells is emphasized.
Abstract: Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios Thus far, dozens of methods have been proposed to quantify cell death-related parameters However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells

2,218 citations



Journal ArticleDOI
TL;DR: Although vector-borne diseases will expand their reach and death tolls, especially among elderly people, will increase because of heatwaves, the indirect effects of climate change on water, food security, and extreme climatic events are likely to have the biggest effect on global health.

2,061 citations


Journal ArticleDOI
TL;DR: Classifying interventions according to component techniques and theoretically derived technique combinations and conducting meta-regression enabled identification of effective components of interventions designed to increase physical activity and healthy eating.
Abstract: Objective: Meta-analyses of behavior change (BC) interventions typically find large heterogeneity in effectiveness and small effects. This study aimed to assess the effectiveness of active BC interventions designed to promote physical activity and healthy eating and investigate whether theoretically specified BC techniques improve outcome. Design: Interventions, evaluated in experimental or quasi-experimental studies, using behavioral and/or cognitive techniques to increase physical activity and healthy eating in adults, were systematically reviewed. Intervention content was reliably classified into 26 BC techniques and the effects of individual techniques, and of a theoretically derived combination of self-regulation techniques, were assessed using meta-regression. Main Outcome Measures: Valid outcomes of physical activity and healthy eating. Results: The 122 evaluations (N 44,747) produced an overall pooled effect size of 0.31 (95% confidence interval 0.26 to 0.36, I 2 69%). The technique, “self-monitoring,” explained the greatest amount of among-study heterogeneity (13%). Interventions that combined selfmonitoring with at least one other technique derived from control theory were significantly more effective than the other interventions (0.42 vs. 0.26). Conclusion: Classifying interventions according to component techniques and theoretically derived technique combinations and conducting meta-regression enabled identification of effective components of interventions designed to increase physical activity and healthy eating.

Journal ArticleDOI
TL;DR: It is demonstrated that an unequivocal role for common genetic variants in the etiology of typical PD and population-specific genetic heterogeneity in this disease is suggested, and supporting evidence that common variation around LRRK2 modulates risk for PD is provided.
Abstract: We performed a genome-wide association study (GWAS) in 1,713 individuals of European ancestry with Parkinson's disease (PD) and 3,978 controls. After replication in 3,361 cases and 4,573 controls, we observed two strong association signals, one in the gene encoding a-synuclein (SNCA; rs2736990, OR = 1.23, P = 2.24 x 10(-16)) and another at the MAPT locus (rs393152, OR = 0.77, P = 1.95 x 10(-16)). We exchanged data with colleagues performing a GWAS in Japanese PD cases. Association to PD at SNCA was replicated in the Japanese GWAS1, confirming this as a major risk locus across populations. We replicated the effect of a new locus detected in the Japanese cohort (PARK16, rs823128, OR = 0.66, P = 7.29 x 10(-8)) and provide supporting evidence that common variation around LRRK2 modulates risk for PD (rs1491923, OR = 1.14, P = 1.55 x 10(-5)). These data demonstrate an unequivocal role for common genetic variants in the etiology of typical PD and suggest population-specific genetic heterogeneity in this disease.

Journal ArticleDOI
TL;DR: Although primary and secondary recycling schemes are well established and widely applied, it is concluded that many of the PSW tertiary and quaternary treatment schemes appear to be robust and worthy of additional investigation.

Proceedings ArticleDOI
04 Nov 2009
TL;DR: In this paper, the authors evaluate datapath validation and adaptive beaconing in CTP Noe, a sensor network tree collection protocol, on both interference-free and interference-prone channels.
Abstract: This paper presents and evaluates two principles for wireless routing protocols. The first is datapath validation: data traffic quickly discovers and fixes routing inconsistencies. The second is adaptive beaconing: extending the Trickle algorithm to routing control traffic reduces route repair latency and sends fewer beacons.We evaluate datapath validation and adaptive beaconing in CTP Noe, a sensor network tree collection protocol. We use 12 different testbeds ranging in size from 20--310 nodes, comprising seven platforms, and six different link layers, on both interference-free and interference-prone channels. In all cases, CTP Noe delivers > 90% of packets. Many experiments achieve 99.9%. Compared to standard beaconing, CTP Noe sends 73% fewer beacons while reducing topology repair latency by 99.8%. Finally, when using low-power link layers, CTP Noe has duty cycles of 3% while supporting aggregate loads of 30 packets/minute.

Journal ArticleDOI
TL;DR: This paper will demonstrate how the understanding of speech perception, one important facet of language, has profited from findings and theory in nonhuman primate studies, and identify roles for different cortical areas in the perceptual processing of speech.
Abstract: Speech and language are considered uniquely human abilities: animals have communication systems, but they do not match human linguistic skills in terms of recursive structure and combinatorial power. Yet, in evolution, spoken language must have emerged from neural mechanisms at least partially available in animals. In this paper, we will demonstrate how our understanding of speech perception, one important facet of language, has profited from findings and theory in nonhuman primate studies. Chief among these are physiological and anatomical studies showing that primate auditory cortex, across species, shows patterns of hierarchical structure, topographic mapping and streams of functional processing. We will identify roles for different cortical areas in the perceptual processing of speech and review functional imaging work in humans that bears on our understanding of how the brain decodes and monitors speech. A new model connects structures in the temporal, frontal and parietal lobes linking speech perception and production.

Journal ArticleDOI
TL;DR: The dopaminergic basis of the range of non-motor symptoms that occur in PD such as depression, apathy, sleep disorders (including rapid-eye movement sleep behaviour disorder), and erectile dysfunction are investigated.
Abstract: Several studies, including work from the Parkinson's disease (PD) non-motor group and others, have established that the non-motor symptoms of PD are common, occur across all stages of PD, are under-reported, and are a key determinant of quality of life. Research suggests that the non-motor symptoms of the disease are frequently unrecognised by clinicians and remain untreated. Even when identified, there is a common perception that many of these symptoms are untreatable. The role of dopaminergic drugs in treating the various non-motor problems of PD, although clinically recognised, has received little attention. In this Review, we investigate the dopaminergic basis of the range of non-motor symptoms that occur in PD such as depression, apathy, sleep disorders (including rapid-eye movement sleep behaviour disorder), and erectile dysfunction. We discuss the evidence that these symptoms are treatable, at least in part, with various dopaminergic strategies and, where relevant, we also refer to the use of deep-brain stimulation of appropriate targets in the brain. This Review provides a comprehensive overview of the management of this challenging aspect of PD.

Journal ArticleDOI
TL;DR: A progress report on the biomedical applications of magnetic nanoparticles since 2003 is presented in this paper, with a focus on magnetic actuation for in vitro non-viral transfection and tissue engineering.
Abstract: A progress report is presented on a selection of scientific, technological and commercial advances in the biomedical applications of magnetic nanoparticles since 2003. Particular attention is paid to (i) magnetic actuation for in vitro non-viral transfection and tissue engineering and in vivo drug delivery and gene therapy, (ii) recent clinical results for magnetic hyperthermia treatments of brain and prostate cancer via direct injection, and continuing efforts to develop new agents suitable for targeted hyperthermia following intravenous injection and (iii) developments in medical sensing technologies involving a new generation of magnetic resonance imaging contrast agents, and the invention of magnetic particle imaging as a new modality. Ongoing prospects are also discussed.

Journal ArticleDOI
TL;DR: Mutations in genes encoding the IL10R subunit proteins were found in patients with early-onset enterocolitis, involving hyperinflammatory immune responses in the intestine, and resulted in disease remission in one patient.
Abstract: Background The molecular cause of inflammatory bowel disease is largely unknown. Methods We performed genetic-linkage analysis and candidate-gene sequencing on samples from two unrelated consanguineous families with children who were affected by early-onset inflammatory bowel disease. We screened six additional patients with early-onset colitis for mutations in two candidate genes and carried out functional assays in patients' peripheral-blood mononuclear cells. We performed an allogeneic hematopoietic stem-cell transplantation in one patient. Results In four of nine patients with early-onset colitis, we identified three distinct homozygous mutations in genes IL10RA and IL10RB, encoding the IL10R1 and IL10R2 proteins, respectively, which form a heterotetramer to make up the interleukin-10 receptor. The mutations abrogate interleukin-10–induced signaling, as shown by deficient STAT3 (signal transducer and activator of transcription 3) phosphorylation on stimulation with interleukin-10. Consistent with this...

Journal ArticleDOI
TL;DR: In this paper, the association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2(P = 1 × 10-23), FGF5 (P=1 × 10 -21), SH2B3(P= 3 × 10−18), MTHFR(MTHFR), c10orf107(P), ZNF652(ZNF652), PLCD3 (P,P = 5 × 10 −9),
Abstract: Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

Journal ArticleDOI
TL;DR: Current knowledge on liposome and nanoparticles offer increased precision in chemotherapeutic targeting of prostate cancer and new avenues for the treatment of breast cancer are reviewed.

Journal ArticleDOI
Brian Yanny1, Constance M. Rockosi2, Heidi Jo Newberg3, Gillian R. Knapp4, Jennifer K. Adelman-McCarthy1, Bonnie Alcorn1, S. Allam1, Carlos Allende Prieto5, Carlos Allende Prieto6, Deokkeun An7, K. S. J. Anderson8, K. S. J. Anderson9, Scott F. Anderson10, Coryn A. L. Bailer-Jones11, Steve Bastian1, Timothy C. Beers12, Eric F. Bell11, Vasily Belokurov13, Dmitry Bizyaev8, Norm Blythe8, John J. Bochanski10, William N. Boroski1, Jarle Brinchmann14, J. Brinkmann8, Howard Brewington8, Larry N. Carey10, Kyle M. Cudworth15, Michael L. Evans10, Nick Evans13, Evalyn Gates15, Boris T. Gänsicke16, Bruce Gillespie8, G. F. Gilmore13, Ada Nebot Gomez-Moran, Eva K. Grebel17, Jim Greenwell10, James E. Gunn4, Cathy Jordan8, Wendell Jordan8, Paul Harding18, Hugh C. Harris, John S. Hendry1, Diana Holder8, Inese I. Ivans4, Željko Ivezić10, Sebastian Jester11, Jennifer A. Johnson7, Stephen M. Kent1, S. J. Kleinman8, Alexei Y. Kniazev11, Jurek Krzesinski8, Richard G. Kron15, Nikolay Kuropatkin1, Svetlana Lebedeva1, Young Sun Lee12, R. French Leger1, Sébastien Lépine19, Steve Levine, Huan Lin1, Dan Long8, Craig P. Loomis4, Robert H. Lupton4, O. Malanushenko8, Viktor Malanushenko8, Bruce Margon2, David Martínez-Delgado11, P. M. McGehee20, Dave Monet, Heather L. Morrison18, Jeffrey A. Munn, Eric H. Neilsen1, Atsuko Nitta8, John E. Norris21, Daniel Oravetz8, Russell Owen10, Nikhil Padmanabhan22, Kaike Pan8, R. S. Peterson1, Jeffrey R. Pier, Jared Platson1, Paola Re Fiorentin11, Paola Re Fiorentin23, Gordon T. Richards24, Hans-Walter Rix11, David J. Schlegel22, Donald P. Schneider25, Matthias R. Schreiber26, Axel Schwope, Valena C. Sibley1, Audrey Simmons8, Stephanie A. Snedden8, J. Allyn Smith27, Larry Stark10, Fritz Stauffer8, Matthias Steinmetz, Christopher Stoughton1, Mark SubbaRao28, Mark SubbaRao15, Alexander S. Szalay29, Paula Szkody10, Aniruddha R. Thakar29, Sivarani Thirupathi12, Douglas L. Tucker1, A. Uomoto30, Daniel E. Vanden Berk25, S. Vidrih17, Yogesh Wadadekar31, Yogesh Wadadekar4, S. Watters8, R. Wilhelm32, Rosemary F. G. Wyse29, Jean Yarger8, Daniel B. Zucker13 
TL;DR: The Sloan Extension for Galactic Understanding and Exploration (SEGUE) Survey as mentioned in this paper obtained approximately 240,000 moderate-resolution spectra from 3900 to 9000 of fainter Milky Way stars (14.0 10 per resolution element).
Abstract: The Sloan Extension for Galactic Understanding and Exploration (SEGUE) Survey obtained {approx}240,000 moderate-resolution (R {approx} 1800) spectra from 3900 {angstrom} to 9000 {angstrom} of fainter Milky Way stars (14.0 10 per resolution element, stellar atmospheric parameters are estimated, including metallicity, surface gravity, and effective temperature. SEGUE obtained 3500 deg{sup 2} of additional ugriz imaging (primarily at low Galactic latitudes) providing precise multicolor photometry ({sigma}(g, r, i) {approx} 2%), ({sigma}(u, z) {approx} 3%) and astrometry ({approx}0.1) for spectroscopic target selection. The stellar spectra, imaging data, and derived parameter catalogs for this survey are publicly available as part of Sloan Digital Sky Survey Data Release 7.

Journal ArticleDOI
TL;DR: The original proposed definition of ACLF was found to withstand the test of time and identify a homogenous group of patients presenting with liver failure, which led to the development of the final AARC consensus.
Abstract: The Asian Pacific Association for the Study of the Liver (APASL) set up a working party on acute-on-chronic liver failure (ACLF) in 2004, with a mandate to develop consensus guidelines on various aspects of ACLF relevant to disease patterns and clinical practice in the Asia-Pacific region. Experts predominantly from the Asia–Pacific region constituted this working party and were requested to identify different issues of ACLF and develop the consensus guidelines. A 2-day meeting of the working party was held on January 22–23, 2008, at New Delhi, India, to discuss and finalize the consensus statements. Only those statements that were unanimously approved by the experts were accepted. These statements were circulated to all the experts and subsequently presented at the Annual Conference of the APASL at Seoul, Korea, in March 2008. The consensus statements along with relevant background information are presented in this review.

Journal ArticleDOI
TL;DR: New guidelines for the nomenclature of the human HSP families, HSPH (HSP110), HSPC (H SP90), HSPA (HSPA70), DNAJ, and HSPB (small HSP) as well as for the human chaperonin families HSPD/E (Hsp60/HSP10) and CCT (TRiC).
Abstract: The expanding number of members in the various human heat shock protein (HSP) families and the inconsistencies in their nomenclature have often led to confusion. Here, we propose new guidelines for the nomenclature of the human HSP families, HSPH (HSP110), HSPC (HSP90), HSPA (HSP70), DNAJ (HSP40), and HSPB (small HSP) as well as for the human chaperonin families HSPD/E (HSP60/HSP10) and CCT (TRiC). The nomenclature is based largely on the more consistent nomenclature assigned by the HUGO Gene Nomenclature Committee and used in the National Center of Biotechnology Information Entrez Gene database for the heat shock genes. In addition to this nomenclature, we provide a list of the human Entrez Gene IDs and the corresponding Entrez Gene IDs for the mouse orthologs.

Journal ArticleDOI
02 Oct 2009-Science
TL;DR: It is shown in mice that deletion of ribosomal S6 protein kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, led to increased life span and resistance to age-related pathologies, such as bone, immune, and motor dysfunction and loss of insulin sensitivity.
Abstract: Caloric restriction (CR) protects against aging and disease, but the mechanisms by which this affects mammalian life span are unclear. We show in mice that deletion of ribosomal S6 protein kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, led to increased life span and resistance to age-related pathologies, such as bone, immune, and motor dysfunction and loss of insulin sensitivity. Deletion of S6K1 induced gene expression patterns similar to those seen in CR or with pharmacological activation of adenosine monophosphate (AMP)–activated protein kinase (AMPK), a conserved regulator of the metabolic response to CR. Our results demonstrate that S6K1 influences healthy mammalian life-span and suggest that therapeutic manipulation of S6K1 and AMPK might mimic CR and could provide broad protection against diseases of aging.

Journal ArticleDOI
TL;DR: In nanopore analytics, individual molecules pass through a single nanopore giving rise to detectable temporary blockades in ionic pore current, which ranges from nucleic acids, peptides, proteins, and biomolecular complexes to organic polymers and small molecules.
Abstract: In nanopore analytics, individual molecules pass through a single nanopore giving rise to detectable temporary blockades in ionic pore current. Reflecting its simplicity, nanopore analytics has gained popularity and can be conducted with natural protein as well as man-made polymeric and inorganic pores. The spectrum of detectable analytes ranges from nucleic acids, peptides, proteins, and biomolecular complexes to organic polymers and small molecules. Apart from being an analytical tool, nanopores have developed into a general platform technology to investigate the biophysics, physicochemistry, and chemistry of individual molecules (critical review, 310 references).

Journal ArticleDOI
TL;DR: The 6dF Galaxy Survey (6dFGS) as discussed by the authors is a combined redshift and peculiar velocity survey over the southern sky (|b| > 10°) which yielded 110 256 new extragalactic redshifts and a new catalogue of 125 071 galaxies.
Abstract: We report the final redshift release of the 6dF Galaxy Survey (6dFGS), a combined redshift and peculiar velocity survey over the southern sky (|b| > 10°). Its 136 304 spectra have yielded 110 256 new extragalactic redshifts and a new catalogue of 125 071 galaxies making near-complete samples with (K, H, J, r_F, b_J) ≤ (12.65, 12.95, 13.75, 15.60, 16.75). The median redshift of the survey is 0.053. Survey data, including images, spectra, photometry and redshifts, are available through an online data base. We describe changes to the information in the data base since earlier interim data releases. Future releases will include velocity dispersions, distances and peculiar velocities for the brightest early-type galaxies, comprising about 10 per cent of the sample. Here we provide redshift maps of the southern local Universe with z ≤ 0.1, showing nearby large-scale structures in hitherto unseen detail. A number of regions known previously to have a paucity of galaxies are confirmed as significantly underdense regions. The URL of the 6dFGS data base is http://www-wfau.roe.ac.uk/6dFGS.

Journal ArticleDOI
TL;DR: In this paper, the authors reviewed the impacts of climate change on UK surface water quality through the lens of UK surface waters and concluded that increased water temperatures will affect chemical reaction kinetics and, combined with degradation in quality, freshwater ecological status.
Abstract: It is now accepted that some human-induced climate change is unavoidable. Potential impacts on water supply have received much attention, but relatively little is known about the concomitant changes in water quality. Projected changes in air temperature and rainfall could affect river flows and, hence, the mobility and dilution of contaminants. Increased water temperatures will affect chemical reaction kinetics and, combined with deteriorations in quality, freshwater ecological status. With increased flows there will be changes in stream power and, hence, sediment loads with the potential to alter the morphology of rivers and the transfer of sediments to lakes, thereby impacting freshwater habitats in both lake and stream systems. This paper reviews such impacts through the lens of UK surface water quality. Widely accepted climate change scenarios suggest more frequent droughts in summer, as well as flash-flooding, leading to uncontrolled discharges from urban areas to receiving water courses and estuaries. Invasion by alien species is highly likely, as is migration of species within the UK adapting to changing temperatures and flow regimes. Lower flows, reduced velocities and, hence, higher water residence times in rivers and lakes will enhance the potential for toxic algal blooms and reduce dissolved oxygen levels. Upland streams could experience increased dissolved organic carbon and colour levels, requiring action at water treatment plants to prevent toxic by-products entering public water supplies. Storms that terminate drought periods will flush nutrients from urban and rural areas or generate acid pulses in acidified upland catchments. Policy responses to climate change, such as the growth of bio-fuels or emission controls, will further impact freshwater quality.

Journal ArticleDOI
12 Jun 2009-Cell
TL;DR: It is shown that the Notch ligand Jagged1 is a potent proangiogenic regulator in mice that antagonizes Dll4-Notch signaling in cells expressing Fringe family glycosyltransferases.

Journal ArticleDOI
TL;DR: It is found that the increase in cortisol following waking (CARi), and the integrated volume of cortisol released over the waking period (CARauc), was positively associated with job stress and general life stress and negatively related to posttraumatic stress syndrome.

Journal ArticleDOI
01 Jun 2009-Placenta
TL;DR: Dilation has a surprisingly modest impact on total blood flow, and so it is suggested the placental pathology associated with deficient conversion is dominated by rheological consequences rather than chronic hypoxia.