Showing papers by "University of Copenhagen published in 2007"
TL;DR: A checklist of items that should be addressed in Reports of Observational Studies in Epidemiology (STROBE) Statement, a general reporting recommendations for descriptive observational studies and studies that investigate associations between exposures and health outcomes is developed.
Abstract: Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalizability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies, and cross-sectional studies, and 4 are specific to each of the 3 study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors, and readers. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, 1 or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated Web site (www.strobe-statement.org) should be helpful resources to improve reporting of observational research.
2,813 citations
TL;DR: The main actions of GLP-1 are to stimulate insulin secretion and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions and acts as an enterogastrone and part of the "ileal brake" mechanism.
Abstract: Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon, the gene which is expressed in ...
2,657 citations
University of Cambridge1, National Institutes of Health2, University of Southern California3, International Agency for Research on Cancer4, Academia Sinica5, Princess Anne Hospital6, St Mary's Hospital7, University of London8, The Breast Cancer Research Foundation9, Wellcome Trust Sanger Institute10, Peter MacCallum Cancer Centre11, QIMR Berghofer Medical Research Institute12, University of Copenhagen13, Curie Institute14, Nofer Institute of Occupational Medicine15, University of Helsinki16, Seoul National University17, University of Ulsan18, Harvard University19, Karolinska Institutet20, Agency for Science, Technology and Research21, Hannover Medical School22, Leiden University23, Erasmus University Rotterdam24, University of Minnesota25, University of Sheffield26, Mayo Clinic27, VU University Amsterdam28, Carlos III Health Institute29, University of Melbourne30, Cancer Council New South Wales31, University of Otago32, Cancer Council Victoria33, Bosch34, University of Tübingen35, German Cancer Research Center36, University of Eastern Finland37
TL;DR: To identify further susceptibility alleles, a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls was conducted, followed by a third stage in which 30 single nucleotide polymorphisms were tested for confirmation.
Abstract: Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2.0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P,1027). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P,0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.
2,288 citations
TL;DR: These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution.
Abstract: Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
2,057 citations
TL;DR: Structures of 13 of these microcrystals all reveal steric zippers, but with variations that expand the range of atomic architectures for amyloid-like fibrils and offer an atomic-level hypothesis for the basis of prion strains.
Abstract: Amyloid fibrils formed from different proteins, each associated with a particular disease, contain a common cross-β spine. The atomic architecture of a spine, from the fibril-forming segment GNNQQNY of the yeast prion protein Sup35, was recently revealed by X-ray microcrystallography. It is a pair of β-sheets, with the facing side chains of the two sheets interdigitated in a dry ‘steric zipper’. Here we report some 30 other segments from fibril-forming proteins that form amyloid-like fibrils, microcrystals, or usually both. These include segments from the Alzheimer’s amyloid-β and tau proteins, the PrP prion protein, insulin, islet amyloid polypeptide (IAPP), lysozyme, myoglobin, α-synuclein and β2-microglobulin, suggesting that common structural features are shared by amyloid diseases at the molecular level. Structures of 13 of these microcrystals all reveal steric zippers, but with variations that expand the range of atomic architectures for amyloid-like fibrils and offer an atomic-level hypothesis for the basis of prion strains. Degenerative diseases such as Alzheimer's and Parkinson's are associated with the precipitation of amyloid fibrils in the brain. The fibrils are remarkably uniform in structure, considering the diversity of the proteins that produce them. Sawaya et al. have now identified 30 short fibril-forming peptides taken from a large range of amyloid diseases and have solved the atomic structures of crystals formed by 13 of them. All the peptides so far examined self-assemble by forming variants of the 'steric zipper', a structural feature first found in the yeast prion protein Sup 35. The zipper may be a key to the strength of amyloid fibrils, and is a prime target for therapeutic intervention. Degenerative diseases such as Alzheimer's or Parkinson's are associated with the misfolding of many diverse proteins, yet the amyloid fibrils formed by all these proteins are similar. David Eisenberg and colleagues have now identified 30 short fibril-forming peptides implicated in a range of amyloid diseases and have solved 13 of their atomic structures, revealing variations in one common feature — the 'steric zipper'.
2,027 citations
TL;DR: The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors and readers.
Abstract: Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalizability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies and cross-sectional studies and four are specific to each of the three study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors and readers.This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, one or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated web site (http://www.strobe-statement.org) should be helpful resources to improve reporting of observational research.
2,020 citations
Ludwig Institute for Cancer Research1, University of Copenhagen2, University of Helsinki3, National Institute for Health and Welfare4, International Agency for Research on Cancer5, Norwegian University of Science and Technology6, Cayetano Heredia University7, Medical University of Warsaw8, Lund University9, Karolinska Institutet10, Boston Children's Hospital11, Emory University12, Indiana University – Purdue University Indianapolis13, Georgia Regents University14, University of Washington15, Johns Hopkins University16, Duke University17, Merck & Co.18
TL;DR: In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV- 16 or HPV -18 than did those inThe placebo group.
Abstract: BACKGROUND: Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV-16 and HPV-18. METHODS: In this randomized, double-blind trial, we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo, administered at day 1, month 2, and month 6. The primary analysis was performed for a per-protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose (month 7). The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer related to HPV-16 or HPV-18. RESULTS: Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo. Vaccine efficacy for the prevention of the primary composite end point was 98% (95.89% confidence interval [CI], 86 to 100) in the per-protocol susceptible population and 44% (95% CI, 26 to 58) in an intention-to-treat population of all women who had undergone randomization (those with or without previous infection). The estimated vaccine efficacy against all high-grade cervical lesions, regardless of causal HPV type, in this intention-to-treat population was 17% (95% CI, 1 to 31). CONCLUSIONS: In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group.
1,904 citations
National Institutes of Health1, Imperial College London2, Aarhus University3, University of Oxford4, University of Wisconsin-Madison5, University of Toronto6, University of California, Los Angeles7, Columbia University8, National Institute of Radiological Sciences9, University of Michigan10, University of Copenhagen11, University of Turku12, VU University Amsterdam13, Brookhaven National Laboratory14, Pfizer15, Washington University in St. Louis16, Indiana University – Purdue University Indianapolis17, University of Pittsburgh18, University of British Columbia19, Emory University20, Johns Hopkins University21, Yale University22
TL;DR: An international group of experts in pharmacokinetic modeling recommends a consensus nomenclature to describe in vivo molecular imaging of reversibly binding radioligands.
Abstract: An international group of experts in pharmacokinetic modeling recommends a consensus nomenclature to describe in vivo molecular imaging of reversibly binding radioligands.
1,858 citations
Versailles Saint-Quentin-en-Yvelines University1, Joseph Fourier University2, Alfred Wegener Institute for Polar and Marine Research3, Reykjavík University4, University of Copenhagen5, University of Bern6, Centre national de la recherche scientifique7, University of Parma8, Université libre de Bruxelles9, University of Trieste10, Max Planck Society11, British Antarctic Survey12
TL;DR: It is suggested that the interplay between obliquity and precession accounts for the variable intensity of interglacial periods in ice core records.
Abstract: A high-resolution deuterium profile is now available along the entire European Project for Ice Coring in Antarctica Dome C ice core, extending this climate record back to marine isotope stage 20.2, ∼800,000 years ago. Experiments performed with an atmospheric general circulation model including water isotopes support its temperature interpretation. We assessed the general correspondence between Dansgaard-Oeschger events and their smoothed Antarctic counterparts for this Dome C record, which reveals the presence of such features with similar amplitudes during previous glacial periods. We suggest that the interplay between obliquity and precession accounts for the variable intensity of interglacial periods in ice core records.
1,723 citations
TL;DR: The significantly expanded PDB2PQR is reported that includes robust standalone command line support, improved pKa estimation via the PROPKA framework, ligand parameterization via PEOE_PB charge methodology, expanded set of force fields and easily incorporated user-defined parameters via XML input files, and improvement of atom addition and optimization code.
Abstract: Real-world observable physical and chemical characteristics are increasingly being calculated from the 3D structures of biomolecules. Methods for calculating pK(a) values, binding constants of ligands, and changes in protein stability are readily available, but often the limiting step in computational biology is the conversion of PDB structures into formats ready for use with biomolecular simulation software. The continued sophistication and integration of biomolecular simulation methods for systems- and genome-wide studies requires a fast, robust, physically realistic and standardized protocol for preparing macromolecular structures for biophysical algorithms. As described previously, the PDB2PQR web server addresses this need for electrostatic field calculations (Dolinsky et al., Nucleic Acids Research, 32, W665-W667, 2004). Here we report the significantly expanded PDB2PQR that includes the following features: robust standalone command line support, improved pK(a) estimation via the PROPKA framework, ligand parameterization via PEOE_PB charge methodology, expanded set of force fields and easily incorporated user-defined parameters via XML input files, and improvement of atom addition and optimization code. These features are available through a new web interface (http://pdb2pqr.sourceforge.net/), which offers users a wide range of options for PDB file conversion, modification and parameterization.
1,680 citations
TL;DR: The six articles of the special feature are introduced and situated within these components of study of land change: observation and monitoring; understanding the coupled system—causes, impacts, and consequences; modeling; and synthesis issues.
Abstract: Land change science has emerged as a fundamental component of global environmental change and sustainability research. This interdisciplinary field seeks to understand the dynamics of land cover and land use as a coupled human-environment system to address theory, concepts, models, and applications relevant to environmental and societal problems, including the intersection of the two. The major components and advances in land change are addressed: observation and monitoring; understanding the coupled system-causes, impacts, and consequences; modeling; and synthesis issues. The six articles of the special feature are introduced and situated within these components of study.
TL;DR: The fate of the modified components, the energetic costs to the cell of replacing such components, as well as strategies to minimize transfer of oxidatively damaged components to the next generation are considered.
Abstract: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced in many places in living cells and at an increased rate during biotic or abiotic stress. ROS and RNS participate in signal transduction, but also modify cellular components and cause dam- age. We first look at the most common ROS and their properties. We then consider the ways in which the cell can regulate their pro- duction and removal. We critically assess current knowledge about modifications of polyunsaturated fatty acids (PUFAs), DNA, carbo- hydrates, and proteins and illustrate this knowledge with case stories wherever possible. Some oxidative breakdown products, e.g., from PUFA, can cause secondary damage. Other oxidation products are secondary signaling molecules. We consider the fate of the modi- fied components, the energetic costs to the cell of replacing such components, as well as strategies to minimize transfer of oxidatively damaged components to the next generation.
TL;DR: Investigation of the association of cumulative exposure to protease inhibitors and nonnucleoside reverse-transcriptase inhibitors with the risk of myocardial infarction found no evidence of such an association for nonn nucleosidereverse-transcriptionase inhibitors; however, the number of person-years of observation for exposure to this class of drug was less than that for Exposure to prote enzyme inhibitors.
Abstract: BACKGROUND: We have previously demonstrated an association between combination antiretroviral therapy and the risk of myocardial infarction. It is not clear whether this association differs according to the class of antiretroviral drugs. We conducted a study to investigate the association of cumulative exposure to protease inhibitors and nonnucleoside reverse-transcriptase inhibitors with the risk of myocardial infarction. METHODS: We analyzed data collected through February 2005 from our prospective observational study of 23,437 patients infected with the human immunodeficiency virus. The incidence rates of myocardial infarction during the follow-up period were calculated, and the associations between myocardial infarction and exposure to protease inhibitors or nonnucleoside reverse-transcriptase inhibitors were determined. RESULTS: Three hundred forty-five patients had a myocardial infarction during 94,469 person-years of observation. The incidence of myocardial infarction increased from 1.53 per 1000 person-years in those not exposed to protease inhibitors to 6.01 per 1000 person-years in those exposed to protease inhibitors for more than 6 years. After adjustment for exposure to the other drug class and established cardiovascular risk factors (excluding lipid levels), the relative rate of myocardial infarction per year of protease-inhibitor exposure was 1.16 (95% confidence interval [CI], 1.10 to 1.23), whereas the relative rate per year of exposure to nonnucleoside reverse-transcriptase inhibitors was 1.05 (95% CI, 0.98 to 1.13). Adjustment for serum lipid levels further reduced the effect of exposure to each drug class to 1.10 (95% CI, 1.04 to 1.18) and 1.00 (95% CI, 0.93 to 1.09), respectively. CONCLUSIONS: Increased exposure to protease inhibitors is associated with an increased risk of myocardial infarction, which is partly explained by dyslipidemia. We found no evidence of such an association for nonnucleoside reverse-transcriptase inhibitors; however, the number of person-years of observation for exposure to this class of drug was less than that for exposure to protease inhibitors.
TL;DR: A hidden Markov model, Phobius, is designed that combines transmembrane topology and signal peptide predictions, and also allows constrained and homology-enriched predictions.
Abstract: When using conventional transmembrane topology and signal peptide predictors, such as TMHMM and SignalP, there is a substantial overlap between these two types of predictions. Applying these methods to five complete proteomes, we found that 30–65% of all predicted signal peptides and 25–35% of all predicted transmembrane topologies overlap. This impairs predictions of 5–10% of the proteome, hence this is an important issue in protein annotation. To address this problem, we previously designed a hidden Markov model, Phobius, that combines transmembrane topology and signal peptide predictions. The method makes an optimal choice between transmembrane segments and signal peptides, and also allows constrained and homologyenriched predictions. We here present a web interface (http:// phobius.cgb.ki.se and http://phobius.binf.ku.dk) to access Phobius.
University of Oslo1, Saarland University2, University of Hull3, Nova Southeastern University4, University of Copenhagen5, University of Gothenburg6, Charles University in Prague7, University of Helsinki8, University of Geneva9, Katholieke Universiteit Leuven10, University of Groningen11, AstraZeneca12
TL;DR: Rosuvastatin did not reduce the primary outcome or the number of deaths from any cause in older patients with systolic heart failure, although the drug did reduce the numberOf cardiovascular hospitalizations and the drugdid not cause safety problems.
Abstract: As compared with the placebo group, patients in the rosuvastatin group had de- creased levels of low-density lipoprotein cholesterol (difference between groups, 45.0%; P<0.001) and of high-sensitivity C-reactive protein (difference between groups, 37.1%; P<0.001). During a median follow-up of 32.8 months, the primary outcome occurred in 692 patients in the rosuvastatin group and 732 in the placebo group (hazard ratio, 0.92; 95% confidence interval (CI), 0.83 to 1.02; P = 0.12), and 728 patients and 759 patients, respectively, died (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P = 0.31). There were no significant differences between the two groups in the coronary outcome or death from cardiovascular causes. In a prespecified secondary analysis, there were fewer hospitalizations for cardiovascular causes in the rosuvastatin group (2193) than in the placebo group (2564) (P<0.001). No excessive episodes of muscle-related or other adverse events occurred in the rosuvastatin group. Conclusions Rosuvastatin did not reduce the primary outcome or the number of deaths from any cause in older patients with systolic heart failure, although the drug did reduce the number of cardiovascular hospitalizations. The drug did not cause safety problems. (ClinicalTrials.gov number, NCT00206310.)
TL;DR: In this paper, the authors provide a cohesive categorisation of the most common sustainability assessment tools within the broader objective of lifting the understanding of tools from the environmentally-focused realm to that of the wider concept of sustainability.
Richard A. Gibbs1, Jeffrey Rogers2, Michael G. Katze3, Roger E. Bumgarner3 +174 more•Institutions (28)
TL;DR: The genome sequence of an Indian-origin Macaca mulatta female is determined and compared with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families.
Abstract: The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.
TL;DR: A unified heuristic which is able to solve five different variants of the vehicle routing problem and shown promising results for a large class of vehicle routing problems with backhauls as demonstrated in Ropke and Pisinger.
TL;DR: It is shown that the human JmjC-domain-containing proteins UTX and JMJD3 demethylate tri-methylated Lys 27 on histone H3, and the results suggest that H3K27me3 dem methylation regulated by UTX/JMJD3 proteins is essential for proper development.
Abstract: The trithorax and the polycomb group proteins are chromatin modifiers, which play a key role in the epigenetic regulation of development, differentiation and maintenance of cell fates. The polycomb repressive complex 2 (PRC2) mediates transcriptional repression by catalysing the di- and tri-methylation of Lys 27 on histone H3 (H3K27me2/me3). Owing to the essential role of the PRC2 complex in repressing a large number of genes involved in somatic processes, the H3K27me3 mark is associated with the unique epigenetic state of stem cells. The rapid decrease of the H3K27me3 mark during specific stages of embryogenesis and stem-cell differentiation indicates that histone demethylases specific for H3K27me3 may exist. Here we show that the human JmjC-domain-containing proteins UTX and JMJD3 demethylate tri-methylated Lys 27 on histone H3. Furthermore, we demonstrate that ectopic expression of JMJD3 leads to a strong decrease of H3K27me3 levels and causes delocalization of polycomb proteins in vivo. Consistent with the strong decrease in H3K27me3 levels associated with HOX genes during differentiation, we show that UTX directly binds to the HOXB1 locus and is required for its activation. Finally mutation of F18E9.5, a Caenorhabditis elegans JMJD3 orthologue, or inhibition of its expression, results in abnormal gonad development. Taken together, these results suggest that H3K27me3 demethylation regulated by UTX/JMJD3 proteins is essential for proper development. Moreover, the recent demonstration that UTX associates with the H3K4me3 histone methyltransferase MLL2 (ref. 8) supports a model in which the coordinated removal of repressive marks, polycomb group displacement, and deposition of activating marks are important for the stringent regulation of transcription during cellular differentiation.
Duke University1, University of Lausanne2, University of Zurich3, Vita-Salute San Raffaele University4, University of Modena and Reggio Emilia5, University College London6, Catholic University of the Sacred Heart7, King's College London8, Murdoch University9, University of Barcelona10, University of Copenhagen11, University of Geneva12, Harvard University13, John Radcliffe Hospital14
TL;DR: Using a whole-genome association strategy, polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set-point period of infection are identified.
Abstract: Understanding why some people establish and maintain effective control of HIV-1 and others do not is a priority in the effort to develop new treatments for HIV/AIDS. Using a whole-genome association strategy, we identified polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set-point period of infection. One of these is found within an endogenous retroviral element and is associated with major histocompatibility allele human leukocyte antigen (HLA)-B*5701, whereas a second is located near the HLA-C gene. An additional analysis of the time to HIV disease progression implicated two genes, one of which encodes an RNA polymerase I subunit. These findings emphasize the importance of studying human genetic variation as a guide to combating infectious agents.
TL;DR: Evidence that aquaporins can channel hydrogen peroxide (H2O2) through specific members of the aquaporin family is presented, the first molecular genetic evidence for the diffusion of H2 O2 through specificMembers of the Aquaporin Family is presented.
TL;DR: Play, affiliative behaviors and some vocalizations appear to be the most promising convenient indicators for assessing positive experiences in laboratory and farm animals under commercial conditions.
TL;DR: An increase in the free cytosolic calcium ([Ca(2+)](c) serves as a potent inducer of macroautophagy and as a target for the antiautophagy action of ER-located Bcl-2.
Harvard University1, Fermilab2, University of California, Berkeley3, Stanford University4, Space Telescope Science Institute5, Johns Hopkins University6, University of Notre Dame7, University of Washington8, Australian National University9, Pontifical Catholic University of Chile10, University of Toronto11, University of Copenhagen12, Texas A&M University13, European Southern Observatory14, Ohio State University15, Stockholm University16, University of Hawaii17
TL;DR: In this paper, a set of constraints on the dark energy equation-of-state parameter w = P/(rho c(2)) were derived using 60 SNe Ia from the ESSENCE supernova survey.
Abstract: We present constraints on the dark energy equation-of-state parameter, w = P/(rho c(2)), using 60 SNe Ia fromthe ESSENCE supernova survey. We derive a set of constraints on the nature of the dark energy assuming a flat universe. By including constraints on (Omega(M), w) from baryon acoustic oscillations, we obtain a value for a static equation-of-state parameter w = -1:05(-0.12)(+0: 13) (stat 1 sigma) +/- 0: 13 (sys) and Omega(M) = 0:274(-0.020)(+0:033) (stat 1 sigma) with a bestfit chi(2)/dof of 0.96. These results are consistent with those reported by the Supernova Legacy Survey from the first year of a similar program measuring supernova distances and redshifts. We evaluate sources of systematic error that afflict supernova observations and present Monte Carlo simulations that explore these effects. Currently, the largest systematic with the potential to affect our measurements is the treatment of extinction due to dust in the supernova host galaxies. Combining our set of ESSENCE SNe Ia with the first-results Supernova Legacy Survey SNe Ia, we obtain a joint constraint of w = -1:07(-0: 09)(+0:09) (stat 1 sigma) +/- 0: 13 ( sys), Omega(M) 0:267(-0:028)(+0:028) (stat 1 sigma) with a best-fit chi(2)/dof of 0.91. The current global SN Ia data alone rule out empty (Omega(M) = 0), matter-only Omega(M) = 0: 3, and Omega(M) = 1 universes at > 4.5 sigma. The current SN Ia data are fully consistent with a cosmological constant.
TL;DR: Cilia are membrane-bounded centriole-derived projections from the cell surface that contain a microtubule cytoskeleton, the ciliary axoneme, surrounded by a ciliary membrane.
Abstract: Cilia are membrane-bounded, centriole-derived projections from the cell surface that contain a microtubule cytoskeleton, the ciliary axoneme, surrounded by a ciliary membrane. Axonemes in multicili- ated cells of mammalian epithelia are 9 + 2, possess dynein arms, and are motile. In contrast, single nonmotile 9 + 0 primary cilia are found on epithelial cells, such as those of the kidney tubule, but also on nonepithelial cells, such as chondrocytes, fibroblasts, and neurons. The ciliary membranes of all cilia contain specific receptors and ion channel proteins that initiate signaling pathways controlling motil- ity and/or linking mechanical or chemical stimuli, including sonic hedgehog and growth factors, to intracellular transduction cascades regulating differentiation, migration, and cell growth during devel- opment and in adulthood. Unique motile 9 + 0 cilia, found during development at the embryonic node, determine left-right asymme- try of the body.
TL;DR: Patients with moderate-to-severe Crohn's disease who had a response to induction therapy with 400 mg of certolizumab pegol were more likely to have a maintained response and a remission at 26 weeks with continued certolIZumab Pegol treatment than with a switch to placebo.
Abstract: Background Certolizumab pegol is a pegylated humanized Fab′ fragment with a high binding affinity for tumor necrosis factor α that does not induce apoptosis of T cells or monocytes. Methods In our randomized, double-blind, placebo-controlled trial, we evaluated the efficacy of certolizumab pegol maintenance therapy in adults with moderate-to-severe Crohn's disease. As induction therapy, 400 mg of certolizumab pegol was administered subcutaneously at weeks 0, 2, and 4. Patients with a clinical response (defined as reduction of at least 100 from the baseline score on the Crohn's Disease Activity Index [CDAI]) at week 6 were stratified according to their baseline C-reactive protein level and were randomly assigned to receive 400 mg of certolizumab pegol or placebo every 4 weeks through week 24, with follow-up through week 26. Results Among patients with a response to induction therapy at week 6 (428 of 668 [64%]), the response was maintained through week 26 in 62% of patients with a baseline C-reactive prote...
TL;DR: In this paper, a large-scale comparison of the transcriptional profiles and 3D cell culture phenotypes of a substantial panel of human breast cancer cell lines is presented, showing that consistent differences in genes encoding signal transduction proteins emerge when even tumor cells are cultured in 3D microenvironments.
TL;DR: The findings suggest that 20 mg per day rimonabant increases the risk of psychiatric adverse events--ie, depressed mood disorders and anxiety-despite depressed mood being an exclusion criterion in these trials.
TL;DR: A Bayesian predictor is developed that identifies novel candidates implicated in disorders such as retinitis pigmentosa, epithelial ovarian cancer, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer disease, type 2 diabetes and coronary heart disease.
Abstract: We performed a systematic, large-scale analysis of human protein complexes comprising gene products implicated in many different categories of human disease to create a phenome-interactome network. This was done by integrating quality-controlled interactions of human proteins with a validated, computationally derived phenotype similarity score, permitting identification of previously unknown complexes likely to be associated with disease. Using a phenomic ranking of protein complexes linked to human disease, we developed a Bayesian predictor that in 298 of 669 linkage intervals correctly ranks the known disease-causing protein as the top candidate, and in 870 intervals with no identified disease-causing gene, provides novel candidates implicated in disorders such as retinitis pigmentosa, epithelial ovarian cancer, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer disease, type 2 diabetes and coronary heart disease. Our publicly available draft of protein complexes associated with pathology comprises 506 complexes, which reveal functional relationships between disease-promoting genes that will inform future experimentation.
TL;DR: A number of pretreatment technologies are under development and being tested in pilot scale for lignocellulose, which is the largest known renewable carbohydrate source as discussed by the authors, but these are not readily accessible to enzymatic hydrolysis and require a pretreatment, which causes an extensive modification of the lignosic structure.
Abstract: The economic dependency on fossil fuels and the resulting effects on climate and environment have put tremendous focus on utilizing fermentable sugars from lignocellulose, the largest known renewable carbohydrate source. The fermentable sugars in lignocellulose are derived from cellulose and hemicelluloses but these are not readily accessible to enzymatic hydrolysis and require a pretreatment, which causes an extensive modification of the lignocellulosic structure. A number of pretreatment technologies are under development and being tested in pilot scale. Hydrolysis of lignocellulose carbohydrates into fermentable sugars requires a number of different cellulases and hemicellulases. The hydrolysis of cellulose is a sequential breakdown of the linear glucose chains, whereas hemicellulases must be capable of hydrolysing branched chains containing different sugars and functional groups. The technology for pretreatment and hydrolysis has been developed to an extent that is close to a commercially viable level. It has become possible to process lignocellulose at high substrate levels and the enzyme performance has been improved. Also the cost of enzymes has been reduced. Still a number of technical and scientific issues within pretreatment and hydrolysis remain to be solved. However, significant improvements in yield and cost reductions are expected, thus making large-scale fermentation of lignocellulosic substrates possible. © 2007 Society of Chemical Industry and John Wiley & Sons, Ltd