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Showing papers by "University of Southern Denmark published in 2011"


Journal ArticleDOI
TL;DR: Cause-specific mortality statistics is a valuable source for the identification of risk factors for poor public health and the quality of the register on causes of death relies mainly upon the correctness of the physicians’ notification and the coding in the National Board of Health.
Abstract: Introduction: Cause-specific mortality statistics is a valuable source for the identification of risk factors for poor public health. Content: Since 1875, the National Board of Health has maintained the register covering all deaths among citizens dying in Denmark, and since 1970 has computerised individual records. Validity and coverage: Classification of cause(s) of deaths is done in accordance to WHO’s rules, since 1994 by ICD-10 codes. A change in coding practices and a low autopsy rate might influence the continuity and validity in cause-specific mortality. Conclusion: The longstanding national registration of causes of death is essential for much research. The quality of the register on causes of death relies mainly upon the correctness of the physicians’ notification and the coding in the National Board of Health.

1,265 citations


Journal ArticleDOI
TL;DR: The determinants most consistently supported by evidence are gender, age, socio-economic position, preferences, parental intake and home availability/accessibility.
Abstract: In order to more effectively promote fruit and vegetable intake among children and adolescents, insight into determinants of intake is necessary. We conducted a review of the literature for potential determinants of fruit and vegetable intake in children and adolescents. Papers were identified from Medline and PsycINFO by using all combinations of the search terms: "fruit(s) or vegetable(s)" and "children or adolescents". Quantitative research examining determinants of fruit and/or vegetable intake among children and adolescents aged 6–18 years were included. The selection and review process was conducted according to a four-step protocol resulting in information on country, population, design, methodology, theoretical basis, instrument used for measuring intake, statistical analysis, included independent variables, and effect sizes. Ninety-eight papers were included. A large number of potential determinants have been studied among children and adolescents. However, for many presumed determinants convincing evidence is lacking, mostly because of paucity of studies. The determinants best supported by evidence are: age, gender, socio-economic position, preferences, parental intake, and home availability/accessibility. Girls and younger children tend to have a higher or more frequent intake than boys and older children. Socio-economic position, preferences, parental intake, and home availability/accessibility are all consistently positively associated with intake. The determinants most consistently supported by evidence are gender, age, socio-economic position, preferences, parental intake and home availability/accessibility. There is a need for internationally comparative, longitudinal, theory-based and multi-level studies taking both personal and environmental factors into account. This paper is published as part of the special Pro Children series in the International Journal of Behavioral Nutrition and Physical Activity. Please see [ http://www.ijbnp.org/content/3/1/26 ] for the relevant editorial.

1,114 citations


Journal ArticleDOI
TL;DR: Therapeutic attenuation of innate immune activation may improve survival in patients with HIV infection and sCD14, a marker of monocyte response to LPS, is an independent predictor of mortality in HIV infection.
Abstract: Methods. This nested case-control study included 74 subjects who died, 120 of whom developed cardiovascular disease and 81 of whom developed AIDS during the Strategies for Management of Anti-Retroviral Therapy (SMART) study with matched control subjects. Intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), soluble CD14 (sCD14), endotoxin core antibody (EndoCAb), and 16S ribosomal DNA (rDNA) were measured in baseline plasma samples. Results. Subjects with the highest quartile of sCD14 levels had a 6-fold higher risk of death than did those in the lowest quartile (95% confidence interval, 2.2‐16.1; P,.001), with minimal change after adjustment for inflammatory markers, CD4 1 T cell count, and HIV RNA level. No other marker was significantly associated with clinical outcomes. I-FABP, LPS, and sCD14 were increased and EndoCAb was decreased in study subjects, compared with healthy volunteers. sCD14 level correlated with levels of IL-6, C-reactive protein, serum amyloid A and D-dimer. Conclusions. sCD14, a marker of monocyte response to LPS, is an independent predictor of mortality in HIV infection. Therapeutic attenuation of innate immune activation may improve survival in patients with HIV infection.

980 citations


Journal ArticleDOI
TL;DR: The determination of the light-quark masses, the form factor, and the decay-constant ratio arising in semileptonic $$K \rightarrow \pi $$K→π transition at zero momentum transfer are reported on.
Abstract: We review lattice results related to pion, kaon, D- and B-meson physics with the aim of making them easily accessible to the particle physics community. More specifically, we report on the determination of the light-quark masses, the form factor f+(0), arising in semileptonic K -> pi transition at zero momentum transfer, as well as the decay constant ratio fK/fpi of decay constants and its consequences for the CKM matrix elements Vus and Vud. Furthermore, we describe the results obtained on the lattice for some of the low-energy constants of SU(2)LxSU(2)R and SU(3)LxSU(3)R Chiral Perturbation Theory and review the determination of the BK parameter of neutral kaon mixing. The inclusion of heavy-quark quantities significantly expands the FLAG scope with respect to the previous review. Therefore, for this review, we focus on D- and B-meson decay constants, form factors, and mixing parameters, since these are most relevant for the determination of CKM matrix elements and the global CKM unitarity-triangle fit. In addition we review the status of lattice determinations of the strong coupling constant alpha_s.

901 citations


Journal ArticleDOI
TL;DR: The Danish Data Archive is introduced and the Act on Processing of Personal Data is presented, which is the legal foundation for analyses of register-based data in Denmark.
Abstract: Danish registers contain information on many important health and social issues. Because all Danish citizens have a unique personal identification number, linkage at the individual level between these nationwide registers and other data sources is possible and feasible. In this paper we briefly introduce selected Danish registers and the data structure and requirements forgetting access to data at Statistics Denmark, which is the main provider of register data. We introduce the Danish Data Archive and briefly present the Act on Processing of Personal Data, which is the legal foundation for analyses of register-based data in Denmark.

838 citations


Journal ArticleDOI
TL;DR: In this article, the authors developed a model of the drivers affecting the implementation of green supply chain management using an Interpretive Structural Modeling (ISM) framework and validated it on a case study involving a manufacturing firm in southern India.
Abstract: Green supply chain management has emerged as an important organizational philosophy to reduce environmental risks. We develop a model of the drivers affecting the implementation of green supply chain management using an Interpretive Structural Modeling (ISM) framework. The various drivers of green supply chain management (GSCM) are identified based on the GSM literature and on consultations with experts in the industry. The model developed is validated on a case study involving a manufacturing firm in southern India.

824 citations


Journal ArticleDOI
01 Apr 2011-Elements
TL;DR: In this paper, a detailed appraisal of the influence of ferruginous seafloor conditions on the evolution of biogeochemical cycles, climate, and the biosphere is increasingly required.
Abstract: The reconstruction of oceanic paleoredox conditions on Earth is essential for investigating links between biospheric oxygenation and major periods of biological innovation and extinction, and for unravelling feedback mechanisms associated with paleoenvironmental change. The occurrence of anoxic, iron-rich (ferruginous) oceanic conditions often goes unrecognized, but refined techniques are currently providing evidence to suggest that ferruginous deep-ocean conditions were likely dominant throughout much of Earth's history. The prevalence of this redox state suggests that a detailed appraisal of the influence of ferruginous conditions on the evolution of biogeochemical cycles, climate, and the biosphere is increasingly required.

747 citations


Journal ArticleDOI
15 Jun 2011-JAMA
TL;DR: While the associations between time spent viewing TV and risk of type 2 diabetes and cardiovascular disease were linear, the risk of all-cause mortality appeared to increase with TV viewing duration of greater than 3 hours per day.
Abstract: Context Prolonged television (TV) viewing is the most prevalent and pervasive sedentary behavior in industrialized countries and has been associated with morbidity and mortality. However, a systematic and quantitative assessment of published studies is not available. Objective To perform a meta-analysis of all prospective cohort studies to determine the association between TV viewing and risk of type 2 diabetes, fatal or nonfatal cardiovascular disease, and all-cause mortality. Data Sources and Study Selection Relevant studies were identified by searches of the MEDLINE database from 1970 to March 2011 and the EMBASE database from 1974 to March 2011 without restrictions and by reviewing reference lists from retrieved articles. Cohort studies that reported relative risk estimates with 95% confidence intervals (CIs) for the associations of interest were included. Data Extraction Data were extracted independently by each author and summary estimates of association were obtained using a random-effects model. Data Synthesis Of the 8 studies included, 4 reported results on type 2 diabetes (175 938 individuals; 6428 incident cases during 1.1 million person-years of follow-up), 4 reported on fatal or nonfatal cardiovascular disease (34 253 individuals; 1052 incident cases), and 3 reported on all-cause mortality (26 509 individuals; 1879 deaths during 202 353 person-years of follow-up). The pooled relative risks per 2 hours of TV viewing per day were 1.20 (95% CI, 1.14-1.27) for type 2 diabetes, 1.15 (95% CI, 1.06-1.23) for fatal or nonfatal cardiovascular disease, and 1.13 (95% CI, 1.07-1.18) for all-cause mortality. While the associations between time spent viewing TV and risk of type 2 diabetes and cardiovascular disease were linear, the risk of all-cause mortality appeared to increase with TV viewing duration of greater than 3 hours per day. The estimated absolute risk differences per every 2 hours of TV viewing per day were 176 cases of type 2 diabetes per 100 000 individuals per year, 38 cases of fatal cardiovascular disease per 100 000 individuals per year, and 104 deaths for all-cause mortality per 100 000 individuals per year. Conclusion Prolonged TV viewing was associated with increased risk of type 2 diabetes, cardiovascular disease, and all-cause mortality.

740 citations


Journal ArticleDOI
01 May 2011-Pm&r
TL;DR: To examine the current evidence regarding the reliability and validity of hand‐held dynamometry for assessment of muscle strength in the clinical setting, a large number of studies using this method have found it to be reliable.
Abstract: Objective To examine the current evidence regarding the reliability and validity of hand-held dynamometry for assessment of muscle strength in the clinical setting. Data Sources A search was conducted of the following databases: Cochrane, MEDLINE, PubMed, PEDro, OTseeker, Index to Chiropractic Literature (ICL), and MANTIS, from inception until January 29, 2010. Study Selection The MeSH subject heading "muscle strength dynamometer" was searched, in isolation and in combination with the text word phrases "hand-held dynamometer" and "isokinetic." Four hundred fifty-four different studies met this search and were reviewed for possible inclusion. Data Extraction Two independent reviewers assessed the quality of the included manuscripts. The PEDro data collection system was used in conjunction with the Cochrane Diagnostic Test Accuracy Description. A third reviewer was used when there was disagreement between the primary reviewers. Data Synthesis Seventeen manuscripts met the inclusion criteria for this review, with a total of 19 studies (2 of the manuscripts involved 2 separate studies) that compared hand-held dynamometry with an identified reference standard (isokinetic muscle strength testing). The results demonstrated minimal differences between hand-held dynamometry and isokinetic testing. Conclusions Considering hand-held dynamometry's ease of use, portability, cost, and compact size, compared with isokinetic devices this instrument can be regarded as a reliable and valid instrument for muscle strength assessment in a clinical setting.

557 citations


Journal ArticleDOI
TL;DR: The criteria for defining progression are now acceptable in clinical trials of recurrent disease as they have since been validated and the GCIG requests that data from all clinical trials using these definitions are made available to GCIG trial centers so that continual validation and improvement can be accomplished.
Abstract: The Gynecological Cancer Intergroup (GCIG) has previously reached consensus regarding the criteria that should be used in clinical trial protocols to define progression-free survival after first-line therapy as well as the criteria to define response to treatment in recurrent disease using the serum marker CA 125 and has specified the situations where these criteria should be used. However, the publications did not include detailed definitions, nor were they written to accommodate the new version of Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) now available. Thus, we recommend that the definitions described later in detail are incorporated into clinical trial protocols to maintain consistency. The criteria for defining progression are now acceptable in clinical trials of recurrent disease as they have since been validated (Pujade-Lauraine, personal communication, 2010). The GCIG requests that data from all clinical trials using these definitions are made available to GCIG trial centers so that continual validation and improvement can be accomplished. These definitions were developed from analyzing patients receiving cytotoxic chemotherapy and have not yet been validated in patients receiving molecular targeting agents.

490 citations


Journal ArticleDOI
TL;DR: In this paper, an epistemological positioning of consumer culture theory research beyond the lived experience of consumers is proposed, which explicitly connects the structuring of macro-social explanatory frameworks with the phenomenology of lived experiences, thereby inscribing the micro-social context accounted for by the consumer in a larger sociohistorical context based on the researcher's theoretica.
Abstract: This paper argues for an epistemological positioning of Consumer Culture Theory (CCT) research beyond the lived experience of consumers. CCT, it is argued, brought sociocultural context to consumer research, not least through the introduction of existential phenomenology as a paradigm for CCT studies. However, it is time to expand the contextualization of lived consumer experiences with another contextualization, this time the one of systemic and structuring influences of market and social systems that is not necessarily felt or experienced by consumers in their daily lives, and therefore not necessarily discursively expressed. There is a need to take into consideration the context of context. We therefore suggest an epistemology for CCT that explicitly connects the structuring of macro-social explanatory frameworks with the phenomenology of lived experiences, thereby inscribing the micro-social context accounted for by the consumer in a larger socio-historical context based on the researcher’s theoretica...

Journal ArticleDOI
TL;DR: McAllister et al. as mentioned in this paper reviewed the current understanding of how manure management influences direct and indirect N 2 O emissions and CH 4 emissions, introduce new data comparing direct N 2O emissions following spreading of a range of manure types by different methods, and highlight some of the mitigations being considered by researchers and policy makers in developed and developing countries.

Journal ArticleDOI
TL;DR: In this paper, Adler et al. present a survey of the authors' work in the field of bioinformatics, including the following authors:Sarah AdlerDavid BasketterStuart CretonOlavi PelkonenJan van BenthemValerie Zuang • Klaus Ejner AndersenAlexandre Angers-LoustauAynur AptulaAnna Bal-PriceEmilio Benfenati • Ulrike BernauerJos BessemsFrederic Y. BoisAlan BoobisEsther BrandonSusanne Bremer • Thomas
Abstract: Sarah AdlerDavid BasketterStuart CretonOlavi PelkonenJan van BenthemValerie Zuang • Klaus Ejner AndersenAlexandre Angers-LoustauAynur AptulaAnna Bal-PriceEmilio Benfenati • Ulrike BernauerJos BessemsFrederic Y. BoisAlan BoobisEsther BrandonSusanne Bremer • Thomas BroschardSilvia CasatiSandra CoeckeRaffaella CorviMark CroninGeorge Daston • Wolfgang DekantSusan FelterElise GrignardUrsula Gundert-RemyTuula HeinonenIan Kimber • Jos KleinjansHannu KomulainenReinhard KreilingJoachim KreysaSofia Batista LeiteGeorge Loizou • Gavin MaxwellPaolo MazzatortaSharon MunnStefan PfuhlerPascal PhrakonkhamAldert Piersma • Albrecht PothPilar PrietoGuillermo RepettoVera RogiersGreet SchoetersMichael Schwarz • Rositsa SerafimovaHanna TahtiEmanuela TestaiJoost van DelftHenk van LoverenMathieu Vinken • Andrew WorthJose ´-Manuel Zaldivar

Journal ArticleDOI
TL;DR: It is shown that the ubiquitous Lon (Long Form Filament) protease and mRNA endonucleases (mRNases) encoded by toxin-antitoxin (TA) loci are required for persistence in Escherichia coli.
Abstract: Bacteria form persisters, individual cells that are highly tolerant to different types of antibiotics. Persister cells are genetically identical to nontolerant kin but have entered a dormant state in which they are recalcitrant to the killing activity of the antibiotics. The molecular mechanisms underlying bacterial persistence are unknown. Here, we show that the ubiquitous Lon (Long Form Filament) protease and mRNA endonucleases (mRNases) encoded by toxin-antitoxin (TA) loci are required for persistence in Escherichia coli. Successive deletion of the 10 mRNase-encoding TA loci of E. coli progressively reduced the level of persisters, showing that persistence is a phenotype common to TA loci. In all cases tested, the antitoxins, which control the activities of the mRNases, are Lon substrates. Consistently, cells lacking lon generated a highly reduced level of persisters. Moreover, Lon overproduction dramatically increased the levels of persisters in wild-type cells but not in cells lacking the 10 mRNases. These results support a simple model according to which mRNases encoded by TA loci are activated in a small fraction of growing cells by Lon-mediated degradation of the antitoxins. Activation of the mRNases, in turn, inhibits global cellular translation, and thereby induces dormancy and persistence. Many pathogenic bacteria known to enter dormant states have a plethora of TA genes. Therefore, in the future, the discoveries described here may lead to a mechanistic understanding of the persistence phenomenon in pathogenic bacteria.

Journal ArticleDOI
TL;DR: Cellular events underlying the pluripotency of human embryonic stem cells (hESCs) are elucidated and a core hESC phosphoproteome of sites with similar robust changes in response to the two distinct treatments is identified.
Abstract: To elucidate cellular events underlying the pluripotency of human embryonic stem cells (hESCs), we performed parallel quantitative proteomic and phosphoproteomic analyses of hESCs during differentiation initiated by a diacylglycerol analog or transfer to media that had not been conditioned by feeder cells. We profiled 6521 proteins and 23,522 phosphorylation sites, of which almost 50% displayed dynamic changes in phosphorylation status during 24 hours of differentiation. These data are a resource for studies of the events associated with the maintenance of hESC pluripotency and those accompanying their differentiation. From these data, we identified a core hESC phosphoproteome of sites with similar robust changes in response to the two distinct treatments. These sites exhibited distinct dynamic phosphorylation patterns, which were linked to known or predicted kinases on the basis of the matching sequence motif. In addition to identifying previously unknown phosphorylation sites on factors associated with differentiation, such as kinases and transcription factors, we observed dynamic phosphorylation of DNA methyltransferases (DNMTs). We found a specific interaction of DNMTs during early differentiation with the PAF1 (polymerase-associated factor 1) transcriptional elongation complex, which binds to promoters of the pluripotency and known DNMT target genes encoding OCT4 and NANOG, thereby providing a possible molecular link for the silencing of these genes during differentiation.

Journal ArticleDOI
Tuomas O. Kilpeläinen1, Lu Qi2, Soren Brage1, Stephen J. Sharp1, Emily Sonestedt3, Ellen W. Demerath4, Tariq Ahmad5, Samia Mora2, Marika Kaakinen6, Camilla H. Sandholt7, Christina Holzapfel8, Christine S. Autenrieth, Elina Hyppönen9, Stéphane Cauchi, Meian He2, Zoltán Kutalik10, Meena Kumari9, Alena Stančáková11, Karina Meidtner, Beverley Balkau, Jonathan T. Tan12, Massimo Mangino13, Nicholas J. Timpson14, Yiqing Song2, M. Carola Zillikens, Kathleen A. Jablonski15, Melissa E. Garcia16, Stefan Johansson17, Jennifer L. Bragg-Gresham18, Ying Wu19, Jana V. van Vliet-Ostaptchouk20, N. Charlotte Onland-Moret21, Esther Zimmermann22, Natalia V. Rivera23, Toshiko Tanaka16, Heather M. Stringham18, Günther Silbernagel24, Stavroula Kanoni25, Mary F. Feitosa26, Soren Snitker27, Jonatan R. Ruiz28, Jeffery Metter16, María Teresa Martínez Larrad29, Mustafa Atalay11, Maarit Hakanen30, Najaf Amin23, Christine Cavalcanti-Proença, Anders Grøntved31, Göran Hallmans32, John-Olov Jansson33, Johanna Kuusisto11, Mika Kähönen, Pamela L. Lutsey4, John J. Nolan22, Luigi Palla1, Oluf Pedersen22, Louis Pérusse34, Frida Renström32, Robert A. Scott1, Dmitry Shungin32, Ulla Sovio35, Tuija Tammelin, Tapani Rönnemaa30, Timo A. Lakka11, Matti Uusitupa11, Manuel Serrano Ríos29, Luigi Ferrucci16, Claude Bouchard36, Aline Meirhaeghe37, Mao Fu27, Mark Walker38, Ingrid B. Borecki26, George Dedoussis25, Andreas Fritsche24, Claes Ohlsson33, Michael Boehnke18, Stefania Bandinelli, Cornelia M. van Duijn, Shah Ebrahim35, Debbie A Lawlor14, Vilmundur Gudnason39, Tamara B. Harris16, Thorkild I. A. Sørensen22, Karen L. Mohlke19, Albert Hofman23, André G. Uitterlinden23, Jaakko Tuomilehto40, Terho Lehtimäki, Olli T. Raitakari30, Bo Isomaa, Pål R. Njølstad17, Jose C. Florez41, Simin Liu42, Andy R Ness14, Tim D. Spector13, E. Shyong Tai12, Philippe Froguel43, Heiner Boeing, Markku Laakso11, Michael Marmot9, Sven Bergmann10, Chris Power9, Kay-Tee Khaw44, Daniel I. Chasman2, Paul M. Ridker2, Torben Hansen31, Keri L. Monda19, Thomas Illig, Marjo-Riitta Järvelin45, Nicholas J. Wareham1, Frank B. Hu2, Leif Groop3, Marju Orho-Melander3, Ulf Ekelund1, Paul W. Franks32, Ruth J. F. Loos1 
TL;DR: In this paper, a meta-analysis of data from 45 studies of adults and nine studies of children and adolescents was conducted to confirm or refute unambiguously whether physical activity attenuates the association of FTO with obesity risk.
Abstract: Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n=218,166) and nine studies of children and adolescents (n=19,268). Methods and Findings: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTOxPA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. Conclusions: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.

Book
14 Feb 2011
TL;DR: Noise and Vibration Analysis is a complete and practical guide that combines both signal processing and modal analysis theory with their practical application in noise and vibration analysis.
Abstract: Noise and Vibration Analysis is a complete and practical guide that combines both signal processing and modal analysis theory with their practical application in noise and vibration analysis. It pr ...

Journal ArticleDOI
TL;DR: An intervention to promote early intensive management of patients with type 2 diabetes was associated with a small, non-significant reduction in the incidence of cardiovascular events and death.

Journal ArticleDOI
TL;DR: It is shown that miRNA-138 (miR-138) modulates osteogenic differentiation of hMSCs and attenuates bone formation in vivo, at least in part by inhibiting the focal adhesion kinase signaling pathway.
Abstract: Elucidating the molecular mechanisms that regulate human stromal (mesenchymal) stem cell (hMSC) differentiation into osteogenic lineage is important for the development of anabolic therapies for treatment of osteoporosis. MicroRNAs (miRNAs) are short, noncoding RNAs that act as key regulators of diverse biological processes by mediating translational repression or mRNA degradation of their target genes. Here, we show that miRNA-138 (miR-138) modulates osteogenic differentiation of hMSCs. miRNA array profiling and further validation by quantitative RT-PCR (qRT-PCR) revealed that miR-138 was down-regulated during osteoblast differentiation of hMSCs. Overexpression of miR-138 inhibited osteoblast differentiation of hMSCs in vitro, whereas inhibition of miR-138 function by antimiR-138 promoted expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Furthermore, overexpression of miR-138 reduced ectopic bone formation in vivo by 85%, and conversely, in vivo bone formation was enhanced by 60% when miR-138 was antagonized. Target prediction analysis and experimental validation by luciferase 3′ UTR reporter assay confirmed focal adhesion kinase, a kinase playing a central role in promoting osteoblast differentiation, as a bona fide target of miR-138. We show that miR-138 attenuates bone formation in vivo, at least in part by inhibiting the focal adhesion kinase signaling pathway. Our findings suggest that pharmacological inhibition of miR-138 by antimiR-138 could represent a therapeutic strategy for enhancing bone formation in vivo.

Journal ArticleDOI
TL;DR: The acetylase inhibitor spermidine and the sirtuin-1 activator resveratrol disrupt the antagonistic network of acetylases and deacetylases that regulate autophagy.
Abstract: Autophagy protects organelles, cells, and organisms against several stress conditions. Induction of autophagy by resveratrol requires the nicotinamide adenine dinucleotide–dependent deacetylase sirtuin 1 (SIRT1). In this paper, we show that the acetylase inhibitor spermidine stimulates autophagy independent of SIRT1 in human and yeast cells as well as in nematodes. Although resveratrol and spermidine ignite autophagy through distinct mechanisms, these compounds stimulate convergent pathways that culminate in concordant modifications of the acetylproteome. Both agents favor convergent deacetylation and acetylation reactions in the cytosol and in the nucleus, respectively. Both resveratrol and spermidine were able to induce autophagy in cytoplasts (enucleated cells). Moreover, a cytoplasm-restricted mutant of SIRT1 could stimulate autophagy, suggesting that cytoplasmic deacetylation reactions dictate the autophagic cascade. At doses at which neither resveratrol nor spermidine stimulated autophagy alone, these agents synergistically induced autophagy. Altogether, these data underscore the importance of an autophagy regulatory network of antagonistic deacetylases and acetylases that can be pharmacologically manipulated.

Journal ArticleDOI
TL;DR: Breast cancer radiotherapy has, at least until recently, increased the risk of developing ischaemic heart disease, pericarditis and valvular disease and women with ischaemia heart disease before breast cancer diagnosis may have incurred higher risks than others.

Journal ArticleDOI
TL;DR: Psoriasis is associated with clinically significant cardiovascular risk in a Danish nationwide cohort study and should be considered as a major risk factor for cardiovascular disease in women.
Abstract: . Ahlehoff O, Gislason GH, Charlot M, Jorgensen CH, Lindhardsen J, Olesen JB, Abildstrom SZ, Skov L, Torp-Pedersen C, Hansen PR. (Copenhagen University Hospital Gentofte, Hellerup; Copenhagen University Hospital Bispebjerg, Copenhagen; National Institute of Public Health, University of Southern Denmark, Copenhagen; Copenhagen University Hospital Gentofte, Hellerup; University of Copenhagen, Copenhagen, Denmark) Psoriasis is associated with clinically significant cardiovascular risk: a Danish nationwide cohort study. J Intern Med2011; 270: 147–157. Objective. The magnitude of the cardiovascular risk from psoriasis and psoriatic arthritis is debated. We therefore investigated the psoriasis-related risk of adverse cardiovascular events and mortality. Design, setting and subjects. We conducted a cohort study of the entire Danish population aged ≥18 years followed from 1997 to 2006 by individual-level linkage of nationwide registers. Psoriasis was defined by prescription claims and classified as severe if patients received hospital-based treatment. Time-dependent Poisson regression models were applied to assess cardiovascular risk in patients with psoriasis and psoriatic arthritis. Main outcome measures. All-cause mortality, cardiovascular mortality and hospitalizations for myocardial infarction (MI), stroke and coronary revascularization were recorded. Results. A total of 34 371 patients with mild psoriasis and 2621 with severe psoriasis, including 607 with psoriatic arthritis, were identified and compared with 4 003 265 controls. The event rates and rate ratios (RRs) of all-cause mortality, cardiovascular death, MI, coronary revascularization, stroke and a composite of MI, stroke and cardiovascular death were increased in patients with psoriasis. The rate ratio increased with disease severity and decreased with age of onset. The overall RRs for the composite endpoint were 1.20 (95% confidence interval [CI] 1.14–1.25) and 1.58 (95% CI 1.36–1.82) for mild and severe psoriasis, respectively. The corresponding RRs for cardiovascular death were 1.14 (95% CI 1.06–1.22) and 1.57 (95% CI1.27–1.94). The risk was similar in patients with severe skin affection alone and those with psoriatic arthritis. Conclusions. Psoriasis is associated with increased risk of adverse cardiovascular events and all-cause mortality. Young age, severe skin affection and/or psoriatic arthritis carry the most risk. Patients with psoriasis may be candidates for early cardiovascular risk factor modification.

Journal ArticleDOI
12 May 2011-Blood
TL;DR: Novel findings show that the expression of CD146 differentiates between perivascular versus endosteal localization of non-hematopoietic BM-MSC populations, which may be useful for the study of the hematopOietic environment.

Journal ArticleDOI
TL;DR: The results suggest that human nuclear exosome degradation pathways comprise modules of spatially organized cofactors that diverge from the yeast model.

Journal ArticleDOI
TL;DR: It was found that lignin concentration in volatile solids (VS) was the strongest predictor of BMP for all the biomass samples and hence the biodegradability of organic material (BD) for biogas production.

Journal ArticleDOI
TL;DR: Embryonic, foetal and adult stem cells in osteogenesis, specific features of bone cells needed to be advantageous for clinical use, and the development of therapeutic biological agents.
Abstract: This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed.

Journal ArticleDOI
TL;DR: Luxury retail draws on the principles of art and magic to assemble the charismatic persona of the creative director and to diffuse his aesthetic ideology to the brand as mentioned in this paper, and it enlists magical and aesthetic principles within and without the store to achieve these ends.

Journal ArticleDOI
TL;DR: This work has employed DNase I hypersensitive site analysis to investigate the genome‐wide changes in chromatin structure that accompany the binding of adipogenic transcription factors and demonstrates that C/EBPβ marks a large number of transcription factor ‘hotspots’ before induction of differentiation and chromatin remodelling and is required for their establishment.
Abstract: Adipogenesis is tightly controlled by a complex network of transcription factors acting at different stages of differentiation. Peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein (C/EBP) family members are key regulators of this process. We have employed DNase I hypersensitive site analysis to investigate the genome-wide changes in chromatin structure that accompany the binding of adipogenic transcription factors. These analyses revealed a dramatic and dynamic modulation of the chromatin landscape during the first hours of adipocyte differentiation that coincides with cooperative binding of multiple early transcription factors (including glucocorticoid receptor, retinoid X receptor, Stat5a, C/EBPβ and -δ) to transcription factor 'hotspots'. Our results demonstrate that C/EBPβ marks a large number of these transcription factor 'hotspots' before induction of differentiation and chromatin remodelling and is required for their establishment. Furthermore, a subset of early remodelled C/EBP-binding sites persists throughout differentiation and is later occupied by PPARγ, indicating that early C/EBP family members, in addition to their well-established role in activation of PPARγ transcription, may act as pioneering factors for PPARγ binding.

Journal ArticleDOI
TL;DR: The report of the hadronic working group of the BOOST2010 workshop held at the University of Oxford in June 2010 as discussed by the authors discusses the potential of hadronic decays of highly boosted particles as an aid for discovery at the LHC and a discussion of tools developed to meet the challenge of reconstructing and isolating these topologies.
Abstract: We present the report of the hadronic working group of the BOOST2010 workshop held at the University of Oxford in June 2010. The first part contains a review of the potential of hadronic decays of highly boosted particles as an aid for discovery at the LHC and a discussion of the status of tools developed to meet the challenge of reconstructing and isolating these topologies. In the second part, we present new results comparing the performance of jet grooming techniques and top tagging algorithms on a common set of benchmark channels. We also study the sensitivity of jet substructure observables to the uncertainties in Monte Carlo predictions.