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Showing papers by "University of Zagreb published in 2010"


Journal ArticleDOI
TL;DR: Genetic loci associated with body mass index map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor, which may provide new insights into human body weight regulation.
Abstract: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

2,632 citations


Journal ArticleDOI
Josée Dupuis1, Josée Dupuis2, Claudia Langenberg, Inga Prokopenko3  +336 moreInstitutions (82)
TL;DR: It is demonstrated that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
Abstract: Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

2,022 citations


Journal ArticleDOI
Hana Lango Allen1, Karol Estrada2, Guillaume Lettre3, Sonja I. Berndt4  +341 moreInstitutions (90)
14 Oct 2010-Nature
TL;DR: It is shown that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait, and indicates that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

1,768 citations


Journal ArticleDOI
TL;DR: This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants.
Abstract: The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

1,267 citations


Journal ArticleDOI
TL;DR: The previously proposed classification criteria for Henoch–Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (C-WG) and c-Takayasu arteritis ( c-TA) are validated.
Abstract: Objectives To validate the previously proposed classification criteria for Henoch–Schonlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA). Methods Step 1: retrospective/prospective web-data collection for children with HSP, c-PAN, c-WG and c-TA with age at diagnosis ≤18 years. Step 2: blinded classification by consensus panel of a representative sample of 280 cases. Step 3: statistical (sensitivity, specificity, area under the curve and κ-agreement) and nominal group technique consensus evaluations. Results 827 patients with HSP, 150 with c-PAN, 60 with c-WG, 87 with c-TA and 52 with c-other were compared with each other. A patient was classified as HSP in the presence of purpura or petechiae (mandatory) with lower limb predominance plus one of four criteria: (1) abdominal pain; (2) histopathology (IgA); (3) arthritis or arthralgia; (4) renal involvement. Classification of c-PAN required a systemic inflammatory disease with evidence of necrotising vasculitis OR angiographic abnormalities of medium-/small-sized arteries (mandatory criterion) plus one of five criteria: (1) skin involvement; (2) myalgia/muscle tenderness; (3) hypertension; (4) peripheral neuropathy; (5) renal involvement. Classification of c-WG required three of six criteria: (1) histopathological evidence of granulomatous inflammation; (2) upper airway involvement; (3) laryngo-tracheo-bronchial involvement; (4) pulmonary involvement (x-ray/CT); (5) antineutrophilic cytoplasmic antibody positivity; (6) renal involvement. Classification of c-TA required typical angiographic abnormalities of the aorta or its main branches and pulmonary arteries (mandatory criterion) plus one of five criteria: (1) pulse deficit or claudication; (2) blood pressure discrepancy in any limb; (3) bruits; (4) hypertension; (5) elevated acute phase reactant. Conclusion European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society propose validated classification criteria for HSP, c-PAN, c-WG and c-TA with high sensitivity/specificity.

1,063 citations


Journal ArticleDOI
TL;DR: Disease-related causes, in particular pulmonary fibrosis, PAH and cardiac causes, accounted for the majority of deaths in SSc.
Abstract: Objectives To determine the causes and predictors of mortality in systemic sclerosis (SSc). Methods Patients with SSc (n=5860) fulfilling the American College of Rheumatology criteria and prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) cohort were analysed. EUSTAR centres completed a structured questionnaire on cause of death and comorbidities. Kaplan-Meier and Cox proportional hazards models were used to analyse survival in SSc subgroups and to identify predictors of mortality. Results Questionnaires were obtained on 234 of 284 fatalities. 55% of deaths were attributed directly to SSc and 41% to non-SSc causes; in 4% the cause of death was not assigned. Of the SSc-related deaths, 35% were attributed to pulmonary fibrosis, 26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes (mainly heart failure and arrhythmias). Among the non-SSc-related causes, infections (33%) and malignancies (31%) were followed by cardiovascular causes (29%). Of the non-SSc-related fatalities, 25% died of causes in which SSc-related complications may have participated (pneumonia, sepsis and gastrointestinal haemorrhage). Independent risk factors for mortality and their HR were: proteinuria (HR 3.34), the presence of PAH based on echocardiography (HR 2.02), pulmonary restriction (forced vital capacity below 80% of normal, HR 1.64), dyspnoea above New York Heart Association class II (HR 1.61), diffusing capacity of the lung (HR 1.20 per 10% decrease), patient age at onset of Raynaud's phenomenon (HR 1.30 per 10 years) and the modified Rodnan skin score (HR 1.20 per 10 score points). Conclusion Disease-related causes, in particular pulmonary fibrosis, PAH and cardiac causes, accounted for the majority of deaths in SSc.

1,010 citations


Journal ArticleDOI
Iris M. Heid1, Anne U. Jackson2, Joshua C. Randall3, Tthomas W. Winkler1  +352 moreInstitutions (90)
TL;DR: A meta-analysis of genome-wide association studies for WHR adjusted for body mass index provides evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
Abstract: Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

869 citations


Journal ArticleDOI
TL;DR: An up-to-date review and a new classification of the existingShape reconstruction using coded structured light techniques and their potentials are presented.

782 citations


Journal ArticleDOI
Anna Köttgen1, Anna Köttgen2, Cristian Pattaro3, Carsten A. Böger4, Christian Fuchsberger3, Matthias Olden4, Nicole L. Glazer5, Afshin Parsa6, Xiaoyi Gao7, Qiong Yang8, Albert V. Smith9, Jeffrey R. O'Connel, Man Li1, Helena Schmidt, Toshiko Tanaka10, Toshiko Tanaka11, Aaron Isaacs12, Shamika Ketkar7, Shih-Jen Hwang10, Andrew D. Johnson10, Abbas Dehghan12, Alexander Teumer13, Guillaume Paré14, Elizabeth J. Atkinson15, Tanja Zeller16, Kurt Lohman17, Marilyn C. Cornelis18, Nicole Probst-Hensch19, Nicole Probst-Hensch20, Florian Kronenberg21, Anke Tönjes22, Caroline Hayward23, Thor Aspelund9, Gudny Eiriksdottir, Lenore J. Launer10, Tamara B. Harris10, Evadnie Rampersaud, Braxton D. Mitchel, Dan E. Arking1, Eric Boerwinkle24, Maksim Struchalin12, Margherita Cavalieri, Andrew B. Singleton10, Francesco Giallauria, Jeffrey Metter, Ian H. de Boer5, Talin Haritunians25, Thomas Lumley5, David S. Siscovick5, Bruce M. Psaty5, M. CarolaZillikens12, Ben A. Oostra12, Mary F. Feitosa7, Michael A. Province7, Mariza de Andrade15, Stephen T. Turner15, Arne Schillert3, Andreas Ziegler3, Philipp S. Wild16, Renate B. Schnabel16, Sandra Wilde16, Thomas Münzel16, Tennille S. Leak26, Thomas Illig, Norman Klopp, Christa Meisinger, H.-Erich Wichmann27, Wolfgang Koenig28, Lina Zgaga29, Tatijana Zemunik30, Ivana Kolcic31, Cosetta Minelli3, Frank B. Hu18, Åsa Johansson32, Wilmar Igl32, Ghazal Zaboli32, Sarah H. Wild29, Alan F. Wright23, Harry Campbell29, David Ellinghaus33, Stefan Schreiber33, Yurii S. Aulchenko12, Janine F. Felix12, Fernando Rivadeneira12, André G. Uitterlinden12, Albert Hofman12, Medea Imboden20, Medea Imboden19, Dorothea Nitsch34, Anita Brandstätter21, Barbara Kollerits21, Lyudmyla Kedenko, Reedik Mägi35, Michael Stumvoll22, Peter Kovacs22, Mladen Boban30, Susan Campbell23, Karlhans Endlich13, Henry Völzke13, Heyo K. Kroemer13, Matthias Nauck13, Uwe Völker13, Ozren Polasek31, Veronique Vitart23, Sunita Badola36, Alex Parker36, Paul M. Ridker18, Sharon L.R. Kardia37, Stefan Blankenberg16, Yongmei Liu17, Gary C. Curhan18, Andre Franke33, Thierry Rochat38, Bernhard Paulweber, Inga Prokopenko35, Wei Wang39, Wei Wang30, Vilmundur Gudnason9, Alan R. Shuldine6, Josef Coresh1, Reinhold E. Schmidt, Luigi Ferrucci, Michael G. Shlipak40, Cornelia M. van Duijn12, Ingrid B. Borecki7, Bernhard K. Krämer41, Igor Rudan29, Ulf Gyllensten32, James F. Wilson29, Jacqueline C. M. Witteman12, Peter P. Pramstaller3, Rainer Rettig13, Nicholas D. Hastie23, Daniel I. Chasman18, Wen Hong L. Kao1, Iris M. Heid4, Caroline S. Fox18, Caroline S. Fox10 
TL;DR: The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry to identify new susceptibility loci for reduced renal function as estimated by serum creatinine, serum cystatin c and CKD.
Abstract: Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m(2); n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide-significant loci (P < 5 x 10(-8)) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.

756 citations


Journal ArticleDOI
Jason Z. Liu1, Federica Tozzi2, Dawn M. Waterworth2, Sreekumar G. Pillai2, Pierandrea Muglia2, Lefkos T. Middleton3, Wade H. Berrettini4, Christopher W. Knouff2, Xin Yuan2, Gérard Waeber5, Peter Vollenweider5, Martin Preisig5, Nicholas J. Wareham6, Jing Hua Zhao6, Ruth J. F. Loos6, Ins Barroso7, Kay-Tee Khaw8, Scott M. Grundy, Philip J. Barter9, Robert W. Mahley10, Antero Kesäniemi11, Ruth McPherson12, John B. Vincent13, John Strauss13, James L. Kennedy13, Anne Farmer14, Peter McGuffin14, Richard O. Day15, Keith Matthews15, Per Bakke16, Amund Gulsvik16, Susanne Lucae17, Marcus Ising17, T. Brueckl17, S. Horstmann17, H.-Erich Wichmann18, Rajesh Rawal, Norbert Dahmen19, Claudia Lamina20, Ozren Polasek21, Lina Zgaga22, Jennifer E. Huffman22, Susan Campbell22, Jaspal S. Kooner3, John C. Chambers3, Mary Susan Burnett23, Joseph M. Devaney23, Augusto D. Pichard23, Kenneth M. Kent23, Lowell F. Satler23, Joseph M. Lindsay23, Ron Waksman23, Stephen E. Epstein23, James F. Wilson22, Sarah H. Wild22, Harry Campbell22, Veronique Vitart22, Muredach P. Reilly4, Mingyao Li4, Liming Qu4, Robert L. Wilensky4, William H. Matthai4, Hakon Hakonarson4, Daniel J. Rader4, Andre Franke24, Michael Wittig24, Arne Schäfer24, Manuela Uda25, Antonio Terracciano26, Xiangjun Xiao27, Fabio Busonero25, Paul Scheet27, David Schlessinger26, David St Clair28, Dan Rujescu18, Gonçalo R. Abecasis29, Hans J. Grabe30, Alexander Teumer30, Henry Völzke30, Astrid Petersmann30, Ulrich John30, Igor Rudan31, Igor Rudan22, Caroline Hayward22, Alan F. Wright22, Ivana Kolcic21, Benjamin J. Wright32, John R. Thompson32, Anthony J. Balmforth33, Alistair S. Hall33, Nilesh J. Samani32, Carl A. Anderson7, Tariq Ahmad, Christopher G. Mathew34, Miles Parkes, Jack Satsangi22, Mark J. Caulfield35, Patricia B. Munroe35, Martin Farrall1, Anna F. Dominiczak36, Jane Worthington, Wendy Thomson, Steve Eyre, Anne Barton, Vincent Mooser2, Clyde Francks1, Clyde Francks2, Jonathan Marchini1 
TL;DR: The Oxford-GlaxoSmithKline study (Ox-GSK) as discussed by the authors performed a genome-wide meta-analysis of SNP association with smoking-related behavioral traits and found an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19) that includes CHRNA5, CHRNA3 and CHRNB4.
Abstract: Smoking is a leading global cause of disease and mortality. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.

568 citations


Journal ArticleDOI
Emmanouela Repapi1, Ian Sayers2, Louise V. Wain1, Paul Burton1, Toby Johnson3, Ma'en Obeidat2, Jing Hua Zhao4, Adaikalavan Ramasamy5, Guangju Zhai6, Veronique Vitart7, Jennifer E. Huffman7, Wilmar Igl8, E Albrecht, Panagiotis Deloukas9, John Henderson10, Raquel Granell10, Wendy L. McArdle10, Alicja R. Rudnicka11, Inês Barroso9, Loos Rjf.4, Nicholas J. Wareham4, Linda Mustelin12, Taina Rantanen13, Ida Surakka14, Ida Surakka12, Medea Imboden15, H E Wichmann16, Ivica Grković16, Stipan Janković16, Lina Zgaga17, Hartikainen A-L.12, Hartikainen A-L.14, Hartikainen A-L.9, Leena Peltonen9, Leena Peltonen12, Leena Peltonen14, Ulf Gyllensten8, Åsa Johansson8, Ghazal Zaboli8, Harry Campbell18, Sarah H. Wild18, James F. Wilson18, Sven Gläser19, Georg Homuth19, Henry Völzke19, Massimo Mangino6, Nicole Soranzo9, Nicole Soranzo6, Tim D. Spector6, Ozren Polasek17, Igor Rudan18, Igor Rudan16, Alan F. Wright7, Markku Heliövaara14, Samuli Ripatti12, Samuli Ripatti14, Anneli Pouta14, Åsa Torinsson Naluai20, Olin A-C.20, Kjell Torén20, Mark E. Cooper21, Alan James22, Lyle J. Palmer22, Lyle J. Palmer21, Aroon D. Hingorani23, S.G. Wannamethee11, Peter H. Whincup11, George Davey Smith10, Shah Ebrahim24, Tricia M. McKeever2, Ian D. Pavord25, Andrew K. MacLeod7, Andrew D. Morris26, David J. Porteous7, Cyrus Cooper27, Cyrus Cooper28, Elaine M. Dennison28, Seif O. Shaheen14, Stefan Karrasch, E Schnabel, Holger Schulz, H Grallert, Nabila Bouatia-Naji29, Jérôme Delplanque29, Philippe Froguel5, Philippe Froguel29, John D Blakey2, John Britton2, Richard W Morris23, John W. Holloway28, Debbie A Lawlor10, Jennie Hui30, Jennie Hui22, Fredrik Nyberg31, Fredrik Nyberg20, Jarvelin M-R.32, Catherine Jackson33, Mika Kähönen32, Jaakko Kaprio14, Jaakko Kaprio12, Nicole Probst-Hensch15, Nicole Probst-Hensch30, Beate Koch19, Caroline Hayward7, David M. Evans10, Paul Elliott34, Paul Elliott5, David P. Strachan11, Ian P. Hall2, Martin D. Tobin1 
TL;DR: Genome-wide association with forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in the SpiroMeta consortium offers mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.
Abstract: Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.

Journal ArticleDOI
Cathy E. Elks1, John R. B. Perry2, Patrick Sulem3, Daniel I. Chasman4  +193 moreInstitutions (49)
TL;DR: A meta-analysis of 32 genome-wide association studies in 87,802 women of European descent found 30 new menarche loci and found suggestive evidence for a further 10 loci, including four previously associated with body mass index and three in or near genes implicated in hormonal regulation.
Abstract: To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.

Journal ArticleDOI
TL;DR: In this article, a complete overview of the work done so far on the research and implementation of dividing wall columns can be found, from early ideas on thermal coupling of distillation columns to practical issues that needed to be solved for their successful implementation.
Abstract: Dividing wall column (DWC) is a single shell, fully thermally coupled distillation column capable of separating mixtures of three or more components into high purity products. Compared to conventional columns-in-series and/or in-parallel configurations a DWC requires much less energy, capital and space. This makes DWC to something that corresponds with the present day idea of sustainable process technology. Based on published papers and patent literature this paper aims to give a complete overview of the work done so far on the research and implementation of DWCs, from early ideas on thermal coupling of distillation columns to practical issues that needed to be solved for their successful implementation. Approaches to short-cut and rigorous simulation, optimization, and control are highlighted, with particular focus on column internals and dimensioning, which is only conceptually considered in academic publications. A survey of relevant patents is included providing information on equipment innovations and application areas of industrial interest. Finally authors look at what is needed on research and engineering side to enable maximization of potential gains by building DWCs for obtaining four or even more products containing two or more partition walls in parallel, which is something not yet attempted in industrial practice.

Journal ArticleDOI
TL;DR: Clinical relevant data is presented on prenatal development of thalamocortical connections in the human brain based on extensive Zagreb Neuroembryological Collection, including more than 500 prenatal human brains stained with various classical neurohistological, as well as modern histochemical and immunohistochemical methods.
Abstract: UNLABELLED The aim of this review is to present clinically relevant data on prenatal development of thalamocortical connections in the human brain. The analysis is based on extensive Zagreb Neuroembryological Collection, including more than 500 prenatal human brains stained with various classical neurohistological, as well as modern histochemical and immunohistochemical methods. The connection of thalamocortical axons during the 'waiting' period with transient cortical subplate zone and subsequent synaptic engagement in the cortical plate is the main connectivity event in the late foetus and preterm infant. This connectivity is the structural substrate for the endogeneous subplate and sensory-driven circuitry generating transient electrical phenomena and may represent a transient network in the developmental history of consciousness. CONCLUSION Findings presented in this review should be considered in the management of pain in preterm infants, in searching for the vulnerability of the subplate zone in diagnostic procedures using the in vivo MRI and in revealing the developmental origin of cognitive and mental disorders.

Journal ArticleDOI
TL;DR: Striking evidences implicating LPO in foetal vascular dysfunction occurring in pre-eclampsia, in renal and liver diseases, as well as their role as cause and consequence to cancer development are addressed.
Abstract: Lipid peroxidation (LPO) product accumulation in human tissues is a major cause of tissular and cellular dysfunction that plays a major role in ageing and most age-related and oxidative stress-related diseases. The current evidence for the implication of LPO in pathological processes is discussed in this review. New data and literature review are provided evaluating the role of LPO in the pathophysiology of ageing and classically oxidative stress-linked diseases, such as neurodegenerative diseases, diabetes and atherosclerosis (the main cause of cardiovascular complications). Striking evidences implicating LPO in foetal vascular dysfunction occurring in pre-eclampsia, in renal and liver diseases, as well as their role as cause and consequence to cancer development are addressed.

Journal ArticleDOI
Nona Sotoodehnia1, Aaron Isaacs2, Paul I.W. de Bakker, Marcus Dörr, Christopher Newton-Cheh3, Christopher Newton-Cheh4, Ilja M. Nolte5, Pim van der Harst5, Martina Müller6, Mark Eijgelsheim2, Alvaro Alonso7, Andrew A. Hicks8, Sandosh Padmanabhan9, Caroline Hayward10, Albert V. Smith11, Ozren Polasek12, Steven Giovannone13, Jingyuan Fu5, Jared W. Magnani14, Jared W. Magnani3, Kristin D. Marciante1, Arne Pfeufer8, Arne Pfeufer15, Sina A. Gharib1, Alexander Teumer, Man Li16, Joshua C. Bis1, Fernando Rivadeneira2, Thor Aspelund11, Anna Köttgen16, Toby Johnson17, Kenneth Rice1, Mark P.S. Sie2, Ying A. Wang3, Ying A. Wang14, Norman Klopp, Christian Fuchsberger8, Sarah H. Wild18, Irene Mateo Leach5, Karol Estrada2, Uwe Völker, Alan F. Wright10, Folkert W. Asselbergs5, Folkert W. Asselbergs19, Jiaxiang Qu13, Aravinda Chakravarti20, Moritz F. Sinner6, Jan A. Kors2, Astrid Petersmann21, Tamara B. Harris3, Elsayed Z. Soliman22, Patricia B. Munroe17, Bruce M. Psaty, Ben A. Oostra2, L. Adrienne Cupples3, L. Adrienne Cupples14, Siegfried Perz, Rudolf A. de Boer5, André G. Uitterlinden2, Henry Völzke, Tim D. Spector23, Fangyu Liu13, Eric Boerwinkle24, Anna F. Dominiczak9, Jerome I. Rotter25, Gé van Herpen2, Daniel Levy3, H-Erich Wichmann6, Wiek H. van Gilst5, Jacqueline C.M. Witteman2, Heyo K. Kroemer, W. H. Linda Kao16, Susan R. Heckbert26, Susan R. Heckbert1, Thomas Meitinger15, Albert Hofman2, Harry Campbell18, Aaron R. Folsom7, Dirk J. van Veldhuisen5, Christine Schwienbacher8, Christine Schwienbacher27, Christopher J. O'Donnell3, Claudia B. Volpato8, Mark J. Caulfield17, John M. C. Connell28, Lenore J. Launer3, Xiaowen Lu5, Lude Franke17, Lude Franke5, Rudolf S N Fehrmann5, Gerard J. te Meerman5, Harry J.M. Groen5, Rinse K. Weersma5, Leonard H. van den Berg19, Cisca Wijmenga5, Roel A. Ophoff29, Roel A. Ophoff19, Gerjan Navis5, Igor Rudan30, Igor Rudan18, Harold Snieder23, Harold Snieder5, James F. Wilson18, Peter P. Pramstaller8, David S. Siscovick1, Thomas J. Wang4, Thomas J. Wang3, Vilmundur Gudnason11, Cornelia M. van Duijn2, Stephan B. Felix, Glenn I. Fishman13, Yalda Jamshidi23, Yalda Jamshidi31, Bruno H. Stricker, Nilesh J. Samani32, Nilesh J. Samani33, Stefan Kääb6, Dan E. Arking20 
TL;DR: It is demonstrated that SCN10A, a candidate gene at the most significantly associated locus in this study, is expressed in the mouse ventricular conduction system, and treatment with a selective SCN 10A blocker prolongs QRS duration.
Abstract: The QRS interval, from the beginning of the Q wave to the end of the S wave on an electrocardiogram, reflects ventricular depolarization and conduction time and is a risk factor for mortality, sudden death and heart failure. We performed a genome-wide association meta-analysis in 40,407 individuals of European descent from 14 studies, with further genotyping in 7,170 additional Europeans, and we identified 22 loci associated with QRS duration (P < 5 × 10(-8)). These loci map in or near genes in pathways with established roles in ventricular conduction such as sodium channels, transcription factors and calcium-handling proteins, but also point to previously unidentified biologic processes, such as kinase inhibitors and genes related to tumorigenesis. We demonstrate that SCN10A, a candidate gene at the most significantly associated locus in this study, is expressed in the mouse ventricular conduction system, and treatment with a selective SCN10A blocker prolongs QRS duration. These findings extend our current knowledge of ventricular depolarization and conduction.

Journal ArticleDOI
TL;DR: Surfactants in the Environment Surfactants are a diverse group of chemicals that are best known for their wide use in detergents and other cleaning products and most of them end up dispersed in different environmental compartments such as soil, water or sediment.
Abstract: Surfactants are a diverse group of chemicals that are best known for their wide use in detergents and other cleaning products. After use, residual surfactants are discharged into sewage systems or directly into surface waters, and most of them end up dispersed in different environmental compartments such as soil, water or sediment. The toxic effects of surfactants on various aquatic organisms are well known. In general, surfactants are present in the environment at levels below toxicity and in Croatia below the national limit. Most surfactants are readily biodegradable and their amount is greatly reduced with secondary treatment in wastewater treatment plants. The highest concern is the release of untreated wastewater or wastewater that has undergone primary treatment alone. The discharge of wastewater polluted with massive quantities of surfactants could have serious effects on the ecosystem. Future studies of surfactant toxicities and biodegradation are necessary to withdraw highly toxic and non-biodegradable compounds from commercial use and replace them with more environmentally friendly ones.

Journal ArticleDOI
TL;DR: In postmenopausal women with osteoporosis, lasofoxifene at a dose of 0.5 mg per day was associated with reduced risks of nonvertebral and vertebral fractures, ER-positive breast cancer, coronary heart disease, and stroke but an increased risk of venous thromboembolic events.
Abstract: Background The effects of lasofoxifene on the risk of fractures, breast cancer, and cardiovascular disease are uncertain. Methods In this randomized trial, we assigned 8556 women who were between the ages of 59 and 80 years and had a bone mineral density T score of –2.5 or less at the femoral neck or spine to receive once-daily lasofoxifene (at a dose of either 0.25 mg or 0.5 mg) or placebo for 5 years. Primary end points were vertebral fractures, estrogen receptor (ER)–positive breast cancer, and nonvertebral fractures; secondary end points included major coronary heart disease events and stroke. Results Lasofoxifene at a dose of 0.5 mg per day, as compared with placebo, was associated with reduced risks of vertebral fracture (13.1 cases vs. 22.4 cases per 1000 person-years; hazard ratio, 0.58; 95% confidence interval [CI], 0.47 to 0.70), nonvertebral fracture (18.7 vs. 24.5 cases per 1000 person-years; hazard ratio, 0.76; 95% CI, 0.64 to 0.91), ER-positive breast cancer (0.3 vs. 1.7 cases per 1000 perso...

Journal ArticleDOI
TL;DR: In this paper, a three-particle mixed-harmonic azimuthal correlator is investigated, which is a P-even observable, but directly sensitive to the charge-separation effect.
Abstract: Parity (P)-odd domains, corresponding to nontrivial topological solutions of the QCD vacuum, might be created during relativistic heavy-ion collisions. These domains are predicted to lead to charge separation of quarks along the orbital momentum of the system created in noncentral collisions. To study this effect, we investigate a three-particle mixed-harmonics azimuthal correlator which is a P-even observable, but directly sensitive to the charge-separation effect. We report measurements of this observable using the STAR detector in Au + Au and Cu + Cu collisions at root s(NN) = 200 and 62 GeV. The results are presented as a function of collision centrality, particle separation in rapidity, and particle transverse momentum. A signal consistent with several of the theoretical expectations is detected in all four data sets. We compare our results to the predictions of existing event generators and discuss in detail possible contributions from other effects that are not related to P violation.

Journal ArticleDOI
TL;DR: From the measurements at the three beam energies, no evidence for a critical point in the QCD phase diagram for μB below 200 MeV is found and the products κσ2 and Sσ are constant as functions of collision centrality.
Abstract: 200 GeV corresponding to baryon chemical potentials (mu(B)) between 200 and 20 MeV. Our measurements of the products kappa sigma(2) and S sigma, which can be related to theoretical calculations sensitive to baryon number susceptibilities and long-range correlations, are constant as functions of collision centrality. We compare these products with results from lattice QCD and various models without a critical point and study the root s(NN) dependence of kappa sigma(2). From the measurements at the three beam energies, we find no evidence for a critical point in the QCD phase diagram for mu(B) below 200 MeV.

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TL;DR: The main goal of this review is to summarize the present understanding of CSF formation and compare this understanding to contradictory experimental results that have been obtained so far, and to try to offer a physiological explanation by which these contradictions could be avoided.

Journal ArticleDOI
TL;DR: In this paper, the effect of the high power ultrasound of 24 kHz frequency on rheological and some physical properties of corn starch was examined, and the results showed a decrease in enthalpy of gelatinization and a significant decrease in consistency coefficient.

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TL;DR: It is suggested that the NSSS may be a useful tool for assessing sexual satisfaction regardless of a person's gender, sexual orientation, and relationship status.
Abstract: The development and bicultural validation of the New Sexual Satisfaction Scale (NSSS)--a 20 item, multidimensional, composite measure of sexual satisfaction--is presented. The development of the scale was based on a five-dimension, conceptual model that emphasized the importance of multiple domains of sexual behavior including sexual sensations, sexual awareness and focus, sexual exchange, emotional closeness, and sexual activity. Scale construction and validation were carried out using seven independent samples with over 2,000 participants aged 18 to 55 in Croatia and the United States. Primary data collection was completed using online survey tools. Analyses did not confirm the proposed conceptual framework but suggested a two-dimensional structure focusing on self ("ego-centered") and the other (a "partner- and sexual activity-centered" factor) domains, each containing items representing all five conceptual dimensions. Scale reliability (k = 20) was satisfactory for all samples, and construct validity was confirmed in both cultures. The NSSS was also found to have acceptable one-month stability. It is suggested that the NSSS may be a useful tool for assessing sexual satisfaction regardless of a person's gender, sexual orientation, and relationship status.

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TL;DR: A clinical practice guide to enteral nutrition support is provided, urging the development and application of procedural protocols that include scrupulous attention to hygiene, as well as regular monitoring by a multidisciplinary nutrition support team to minimise the risk of EN-associated complications.
Abstract: Enteral nutrition support (ENS) involves both the delivery of nutrients via feeding tubes and the provision of specialised oral nutritional supplements. ENS is indicated in a patient with at least a partially functioning digestive tract when oral intake is inadequate or intake of normal food is inappropriate to meet the patients' needs. The aim of this comment by the Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition is to provide a clinical practice guide to ENS, based on the available evidence and the clinical expertise of the authors. Statements and recommendations are presented, and future research needs highlighted, with a particular emphasis placed on a practical approach to ENS.Among the wide array of enteral formulations, standard polymeric feeds based on cow's-milk protein with fibre and age adapted for energy and nutrient content are suitable for most paediatric patients. Whenever possible, intragastric is preferred to postpyloric delivery of nutrients, and intermittent feeding is preferred to continuous feeding because it is more physiological. An anticipated duration of enteral nutrition (EN) exceeding 4 to 6 weeks is an indication for gastrostomy or enterostomy. Among the various gastrostomy techniques available, percutaneous endoscopic gastrostomy is currently the first option. In general, both patients and caregivers express satisfaction with this procedure, although it is associated with a number of well-recognised complications. We strongly recommend the development and application of procedural protocols that include scrupulous attention to hygiene, as well as regular monitoring by a multidisciplinary nutrition support team to minimise the risk of EN-associated complications.

Book
29 Apr 2010
TL;DR: Boundary potential theory for Schr#x00F6 dinger operators based on fractional Laplacian is proposed in this article, where the potential theory of subordinate Brownian motion is applied to the potential potential theory.
Abstract: Boundary Potential Theory for Schr#x00F6 dinger Operators Based on Fractional Laplacian.- Nontangential Convergence for #x03B1 -harmonic Functions.- Eigenvalues and Eigenfunctions for Stable Processes.- Potential Theory of Subordinate Brownian Motion.

Journal ArticleDOI
02 Apr 2010-Science
TL;DR: The authors reported the observation of antihypertritons-comprising an antiproton, an antineutron, and an antilambda hyperon-produced by colliding gold nuclei at high energy.
Abstract: Nuclear collisions recreate conditions in the universe microseconds after the Big Bang. Only a very small fraction of the emitted fragments are light nuclei, but these states are of fundamental interest. We report the observation of antihypertritons-comprising an antiproton, an antineutron, and an antilambda hyperon-produced by colliding gold nuclei at high energy. Our analysis yields 70 +/- 17 antihypertritons (3/Lambda(H) over bar) and 157 +/- 30 hypertritons ((3)(Lambda)H). The measured yields of (3)(Lambda)H (3/Lambda(H) over bar) and (3)He ((3)(He) over bar) are similar, suggesting an equilibrium in coordinate and momentum space populations of up, down, and strange quarks and antiquarks, unlike the pattern observed at lower collision energies. The production and properties of antinuclei, and of nuclei containing strange quarks, have implications spanning nuclear and particle physics, astrophysics, and cosmology.

Journal Article
TL;DR: The potential of using bacteriocins of lactic acid bacteria, primarily used as biopreservatives, represents a perspective, alternative antimicrobial strategy for continuously increasing problem with antibiotic resistance.
Abstract: Summary The antimicrobial activity of industrially important lactic acid bacteria as starter cultures and probiotic bacteria is the main subject of this review. This activity has been attributed to the production of metabolites such as organic acids (lactic and acetic acid), hydrogen peroxide, ethanol, diacetyl, acetaldehyde, acetoine, carbon dioxide, reuterin, reutericyclin and bacteriocins. The potential of using bacteriocins of lactic acid bacteria, primarily used as biopreservatives, represents a perspective, alternative antimicrobial strategy for continuously increasing problem with antibiotic resistance. Another strategy in resolving this problem is an application of probiotics for different gastrointestinal and urogenital infection therapies.

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TL;DR: In this paper, the authors adopt the utilitarian view of volunteering as a starting point: they posit that for an undergraduate student population volunteering is motivated by career enhancing and job prospects, and they hypothesize that in those countries where volunteering signals positive characteristics of students and helps advance their careers, their volunteer participation will be higher.
Abstract: This research adopts the utilitarian view of volunteering as a starting point: we posit that for an undergraduate student population volunteering is motivated by career enhancing and job prospects. We hypothesize that in those countries where volunteering signals positive characteristics of students and helps advance their careers, their volunteer participation will be higher. Furthermore, regardless of the signaling value of volunteering, those students who volunteer for utilitarian reasons will be more likely to volunteer but will exhibit less time-intensive volunteering. Using survey data from 12 countries (n = 9,482), we examine our hypotheses related to motivations to volunteer, volunteer participation, and country differences. Findings suggest that students motivated to volunteer for building their resumes do not volunteer more than students with other motives. However, in countries with a positive signaling value of volunteering, volunteering rates are significantly higher. As expected, students motivated by resume building motivations have a lower intensity of volunteering.

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TL;DR: A novel approach combining genome-wide association and high-throughput glycomics analysis of 2,705 individuals in three population cohorts showed that common variants in the Hepatocyte Nuclear Factor 1α (HNF1α) and fucosyltransferase genes FUT6 and FUT8 influence N-glycan levels in human plasma.
Abstract: Over half of all proteins are glycosylated, and alterations in glycosylation have been observed in numerous physiological and pathological processes. Attached glycans significantly affect protein function; but, contrary to polypeptides, they are not directly encoded by genes, and the complex processes that regulate their assembly are poorly understood. A novel approach combining genome-wide association and high-throughput glycomics analysis of 2,705 individuals in three population cohorts showed that common variants in the Hepatocyte Nuclear Factor 1α (HNF1α) and fucosyltransferase genes FUT6 and FUT8 influence N-glycan levels in human plasma. We show that HNF1α and its downstream target HNF4α regulate the expression of key fucosyltransferase and fucose biosynthesis genes. Moreover, we show that HNF1α is both necessary and sufficient to drive the expression of these genes in hepatic cells. These results reveal a new role for HNF1α as a master transcriptional regulator of multiple stages in the fucosylation process. This mechanism has implications for the regulation of immunity, embryonic development, and protein folding, as well as for our understanding of the molecular mechanisms underlying cancer, coronary heart disease, and metabolic and inflammatory disorders.

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TL;DR: A broad variation in the antibacterial properties of investigated essential oils was observed, while Ocimum americanum and OCimum x citriodorum essential oils were the most effective against Enterococcus faecalis, Enterococus faecium, P. vulgaris, S. aureus and S. epidermis.