Showing papers by "University of Southern Denmark published in 2005"
TL;DR: It is reported that PAI values obtained at different concentrations of serum albumin show a linear relationship with the logarithm of protein concentration in LC-MS/MS experiments, and the values of emPAI are suggested that they should be reported in large scale proteomic identification projects.
1,989 citations
TL;DR: In postmenopausal women with endocrine-responsive breast cancer, adjuvant treatment with letrozole, as compared with tamoxifen, reduced the risk of recurrent disease, especially at distant sites.
Abstract: Background The aromatase inhibitor letrozole is a more effective treatment for metastatic breast cancer and more effective in the neoadjuvant setting than tamoxifen. We compared letrozole with tamoxifen as adjuvant treatment for steroid-hormone-receptor-positive breast cancer in postmenopausal women. Methods The Breast International Group (BIG) 1-98 study is a randomized, phase 3, double-blind trial that compared five years of treatment with various adjuvant endocrine therapy regimens in postmenopausal women with hormone-receptor-positive breast cancer: letrozole, letrozole followed by tamoxifen, tamoxifen, and tamoxifen followed by letrozole. This analysis compares the two groups assigned to receive letrozole initially with the two groups assigned to receive tamoxifen initially; events and follow-up in the sequential-treatment groups were included up to the time that treatments were switched. Results A total of 8010 women with data that could be assessed were enrolled, 4003 in the letrozole group and 4007 in the tamoxifen group. After a median follow-up of 25.8 months, 351 events had occurred in the letrozole group and 428 events in the tamoxifen group, with five-year disease-free survival estimates of 84.0 percent and 81.4 percent, respectively. As compared with tamoxifen, letrozole significantly reduced the risk of an event ending a period of disease-free survival (hazard ratio, 0.81; 95 percent confidence interval, 0.70 to 0.93; P=0.003), especially the risk of distant recurrence (hazard ratio, 0.73; 95 percent confidence interval, 0.60 to 0.88; P=0.001). Thromboembolism, endometrial cancer, and vaginal bleeding were more common in the tamoxifen group. Women given letrozole had a higher incidence of skeletal and cardiac events and of hypercholesterolemia. Conclusions In postmenopausal women with endocrine-responsive breast cancer, adjuvant treatment with letrozole, as compared with tamoxifen, reduced the risk of recurrent disease, especially at distant sites. (ClinicalTrials.gov number, NCT00004205.)
1,532 citations
TL;DR: This work demonstrates sub-ppm mass accuracy on a linear ion trap coupled via a radio frequency-only storage trap to the orbitrap mass spectrometer (LTQ Orbitrap), and introduces a variable mass tolerance to improve certainty of peptide and small molecule identification.
1,521 citations
TL;DR: This work reports a highly selective enrichment procedure for phosphorylated peptides based on TiO2microcolumns and peptide loading in 2,5-dihydroxybenzoic acid (DHB), and demonstrates that this new procedure was more selective for binding phosphorylation peptides than IMAC using MALDI mass spectrometry.
1,489 citations
TL;DR: The data establish a quantitative proteomic approach for the temporal characterization of protein flux through cellular organelles and demonstrate that the nucleolar proteome changes significantly over time in response to changes in cellular growth conditions.
Abstract: The nucleolus is a key organelle that coordinates the synthesis and assembly of ribosomal subunits and forms in the nucleus around the repeated ribosomal gene clusters. Because the production of ribosomes is a major metabolic activity, the function of the nucleolus is tightly linked to cell growth and proliferation, and recent data suggest that the nucleolus also plays an important role in cell-cycle regulation, senescence and stress responses. Here, using mass-spectrometry-based organellar proteomics and stable isotope labelling, we perform a quantitative analysis of the proteome of human nucleoli. In vivo fluorescent imaging techniques are directly compared to endogenous protein changes measured by proteomics. We characterize the flux of 489 endogenous nucleolar proteins in response to three different metabolic inhibitors that each affect nucleolar morphology. Proteins that are stably associated, such as RNA polymerase I subunits and small nuclear ribonucleoprotein particle complexes, exit from or accumulate in the nucleolus with similar kinetics, whereas protein components of the large and small ribosomal subunits leave the nucleolus with markedly different kinetics. The data establish a quantitative proteomic approach for the temporal characterization of protein flux through cellular organelles and demonstrate that the nucleolar proteome changes significantly over time in response to changes in cellular growth conditions.
1,102 citations
TL;DR: Evidence now indicates that toxin–antitoxin loci provide a control mechanism that helps free-living prokaryotes cope with nutritional stress.
Abstract: Although toxin-antitoxin gene cassettes were first found in plasmids, recent database mining has shown that these loci are abundant in free-living prokaryotes, including many pathogenic bacteria. For example, Mycobacterium tuberculosis has 38 chromosomal toxin-antitoxin loci, including 3 relBE and 9 mazEF loci. RelE and MazF are toxins that cleave mRNA in response to nutritional stress. RelE cleaves mRNAs that are positioned at the ribosomal A-site, between the second and third nucleotides of the A-site codon. It has been proposed that toxin-antitoxin loci function in bacterial programmed cell death, but evidence now indicates that these loci provide a control mechanism that helps free-living prokaryotes cope with nutritional stress.
991 citations
TL;DR: In this paper, the development of a sequential extraction procedure for iron in modern and ancient sediments is presented, which recognizes seven operationally derived iron pools: (1) carbonate associated Fe (Fe carb ), including siderite and ankerite; (2) easily reducible oxides (Fe ox1 ), including ferrihydrite and lepidocrocite; and (3) reducible Oxides(Fe ox2 ), including goethite, hematite and akaganeite, (4) magnetite (Fe mag ); (5)
975 citations
TL;DR: In this paper, a review of the Precambrian history of atmospheric oxygen is presented, starting with a brief discussion of the possible nature and magnitude of life before the evolution of oxygenic photosynthesis, followed by a summary of the various lines of evidence constraining oxygen levels through time.
Abstract: ▪ Abstract This paper reviews the Precambrian history of atmospheric oxygen, beginning with a brief discussion of the possible nature and magnitude of life before the evolution of oxygenic photosynthesis. This is followed by a summary of the various lines of evidence constraining oxygen levels through time, resulting in a suggested history of atmospheric oxygen concentrations. Also reviewed are the various processes regulating oxygen concentrations, and several models of Precambrian oxygen evolution are presented. A sparse geologic record, combined with uncertainties as to its interpretation, yields only a fragmentary and imprecise reading of atmospheric oxygen evolution. Nevertheless, oxygen levels have increased through time, but not monotonically, with major and fascinating swings to both lower and higher levels.
909 citations
TL;DR: Observations strongly suggest that TA loci are mobile cassettes that move frequently within and between chromosomes and also lend support to the hypothesis thatTA loci function as stress-response elements beneficial to free-living prokaryotes.
Abstract: Prokaryotic chromosomes code for toxin-antitoxin (TA) loci, often in multiple copies. In E.coli, experimental evidence indicates that TA loci are stress-response elements that help cells survive unfavorable growth conditions. The first gene in a TA operon codes for an antitoxin that combines with and neutralizes a regulatory 'toxin', encoded by the second gene. RelE and MazF toxins are regulators of translation that cleave mRNA and function, in interplay with tmRNA, in quality control of gene expression. Here, we present the results from an exhaustive search for TA loci in 126 completely sequenced prokaryotic genomes (16 archaea and 110 bacteria). We identified 671 TA loci belonging to the seven known TA gene families. Surprisingly, obligate intracellular organisms were devoid of TA loci, whereas free-living slowly growing prokaryotes had particularly many (38 in Mycobacterium tuberculosis and 43 in Nitrosomonas europaea). In many cases, TA loci were clustered and closely linked to mobile genetic elements. In the most extreme of these cases, all 13 TA loci of Vibrio cholerae were bona fide integron elements located in the V.cholerae mega-integron. These observations strongly suggest that TA loci are mobile cassettes that move frequently within and between chromosomes and also lend support to the hypothesis that TA loci function as stress-response elements beneficial to free-living prokaryotes.
877 citations
TL;DR: Of more than 700 identified phosphopeptides, 139 were differentially regulated at least 2-fold in response to mating pheromone and among these regulated proteins were components belonging to the mitogen-activated protein kinase signaling pathway and to downstream processes including transcriptional regulation, the establishment of polarized growth, and the regulation of the cell cycle.
808 citations
TL;DR: The results demonstrate that system‐wide mapping of peptide‐protein interactions sites is possible, and suggest shared and unique roles of ErbB‐receptor family members in downstream signaling.
Abstract: Interactions between short modified peptide motifs and modular protein domains are central events in cell signal-transduction. We determined interaction partners to all cytosolic tyrosine residues of the four members of the ErbB-receptor family in an unbiased fashion by quantitative proteomics using pull-down experiments with pairs of phosphorylated and nonphosphorylated synthetic peptides. Each receptor had characteristic preferences for interacting proteins and most interaction partners had multiple binding sites on each receptor. EGFR and ErbB4 had several docking sites for Grb2, while ErbB3 was characterized by six binding sites for PI3K. We identified STAT5 as a direct binding partner to EGFR and ErbB4 and discovered new recognition motifs for Shc and STAT5. The overall pattern of interaction partners of EGFR and ErbB4 suggests similar roles during signaling through their respective ligands. Phosphorylation kinetics of several tyrosine resides was measured by mass spectrometry and correlated with interaction partner preference. Our results demonstrate that system-wide mapping of peptide-protein interactions sites is possible, and suggest shared and unique roles of ErbB-receptor family members in downstream signaling.
TL;DR: The role of drinking-water nitrate exposure as a risk factor for specific cancers, reproductive outcomes, and other chronic health effects must be studied more thoroughly before changes to the regulatory level for nitrate in drinking water can be considered.
Abstract: Human alteration of the nitrogen cycle has resulted in steadily accumulating nitrate in our water resources. The U.S. maximum contaminant level and World Health Organization guidelines for nitrate in drinking water were promulgated to protect infants from developing methemoglobinemia, an acute condition. Some scientists have recently suggested that the regulatory limit for nitrate is overly conservative; however, they have not thoroughly considered chronic health outcomes. In August 2004, a symposium on drinking-water nitrate and health was held at the International Society for Environmental Epidemiology meeting to evaluate nitrate exposures and associated health effects in relation to the current regulatory limit. The contribution of drinking-water nitrate toward endogenous formation of N-nitroso compounds was evaluated with a focus toward identifying subpopulations with increased rates of nitrosation. Adverse health effects may be the result of a complex interaction of the amount of nitrate ingested, the concomitant ingestion of nitrosation cofactors and precursors, and specific medical conditions that increase nitrosation. Workshop participants concluded that more experimental studies are needed and that a particularly fruitful approach may be to conduct epidemiologic studies among susceptible subgroups with increased endogenous nitrosation. The few epidemiologic studies that have evaluated intake of nitrosation precursors and/or nitrosation inhibitors have observed elevated risks for colon cancer and neural tube defects associated with drinking-water nitrate concentrations below the regulatory limit. The role of drinking-water nitrate exposure as a risk factor for specific cancers, reproductive outcomes, and other chronic health effects must be studied more thoroughly before changes to the regulatory level for nitrate in drinking water can be considered.
TL;DR: It is suggested that the chaperonin system may have facilitated the evolution of this fold into a versatile platform for the implementation of numerous enzymatic functions.
TL;DR: The bacteria conducting anammox are highly specialized and appear to belong to the Planctomycetales, and it may be responsible for up to 50% of the global removal of fixed nitrogen from the oceans.
TL;DR: The Actiheart is technically reliable and valid but further studies are needed to assess validity in other activities and during free-living.
Abstract: Accurate quantification of physical activity energy expenditure is a key part of the effort to understand disorders of energy metabolism. The Actiheart, a combined heart rate (HR) and movement sensor, is designed to assess physical activity in populations. To examine aspects of Actiheart reliability and validity in mechanical settings and during walking and running. In eight Actiheart units, technical reliability (coefficients of variation, CV) and validity for movement were assessed with sinusoid accelerations (0.1–20 m/s2) and for HR by simulated R-wave impulses (25–250 bpm). Agreement between Actiheart and ECG was determined during rest and treadmill locomotion (3.2–12.1 km/h). Walking and running intensity (in J/min/kg) was assessed with indirect calorimetry in 11 men and nine women (26–50 y, 20–29 kg/m2) and modelled from movement, HR, and movement+HR by multiple linear regression, adjusting for sex. Median intrainstrument CV was 0.5 and 0.03% for movement and HR, respectively. Corresponding interinstrument CV values were 5.7 and 0.03% with some evidence of heteroscedasticity for movement. The linear relationship between movement and acceleration was strong (R2=0.99, P 0.84, P<0.001) but significantly highest when combining HR and movement (SEE<1 MET). The Actiheart is technically reliable and valid. Walking and running intensity may be estimated accurately but further studies are needed to assess validity in other activities and during free-living. The study received financial support from the Wellcome Trust and SB was supported by a scholarship from Unilever, UK.
TL;DR: It is found that the differentiation of human mesenchymal stem cells into bone-forming cells is stimulated by epidermal growth factor but not platelet-derived growth factor (PDGF).
Abstract: Closely related signals often lead to very different cellular outcomes. We found that the differentiation of human mesenchymal stem cells into bone-forming cells is stimulated by epidermal growth factor (EGF) but not platelet-derived growth factor (PDGF). We used mass spectrometry-based proteomics to comprehensively compare proteins that were tyrosine phosphorylated in response to EGF and PDGF and their associated partners. More than 90% of these signaling proteins were used by both ligands, whereas the phosphatidylinositol 3-kinase (PI3K) pathway was exclusively activated by PDGF, implicating it as a possible control point. Indeed, chemical inhibition of PI3K in PDGF-stimulated cells removed the differential effect of the two growth factors, bestowing full differentiation effect onto PDGF. Thus, quantitative proteomics can directly compare entire signaling networks and discover critical differences capable of changing cell fate.
TL;DR: In this article, a panel of 67 countries attempting to explain differences in self-reported levels of happiness by reference to, amongst other things, temperature and precipitation was analyzed using a panel-corrected least squares approach.
TL;DR: The inherent problems associated with applying dummy coding when including a fixed comparator in a discrete choice experiment are discussed, and the misinterpretations that may arise if the analyst is not aware of the problem are illustrated.
Abstract: This paper discusses the inherent problems associated with applying dummy coding when including a fixed comparator in a discrete choice experiment, and seeks to illustrate the misinterpretations that may arise if the analyst is not aware of the problem. This note provides two examples of possible misinterpretations with dummy coding and how it is solved with the use of effects coding.
TL;DR: The structure of the ribosome has recently been determined by X-ray crystallography, revealing the molecular details of the antibiotic-binding sites and providing insight as to how existing drugs might be derivatized (or novel drugs created) to improve binding and circumvent resistance.
Abstract: Many clinically useful antibiotics exert their antimicrobial effects by blocking protein synthesis on the bacterial ribosome. The structure of the ribosome has recently been determined by X-ray crystallography, revealing the molecular details of the antibiotic-binding sites. The crystal data explain many earlier biochemical and genetic observations, including how drugs exercise their inhibitory effects, how some drugs in combination enhance or impede each other's binding, and how alterations to ribosomal components confer resistance. The crystal structures also provide insight as to how existing drugs might be derivatized (or novel drugs created) to improve binding and circumvent resistance.
TL;DR: Bibliometric studies have many pitfalls; technical skill, critical sense and a precise knowledge about the examined scientific domain are required to carry out and interpret bibliometric investigations correctly.
Abstract: Bibliometric studies are increasingly being used for research assessment Bibliometric indicators are strongly methodology-dependent but for all of them, various types of data normalization are an indispensable requirement Bibliometric studies have many pitfalls; technical skill, critical sense and a precise knowledge about the examined scientific domain are required to carry out and interpret bibliometric investigations correctly
TL;DR: Most degenerative disc “abnormalities” were moderately associated with LBP and the strongest associations were noted for Modic changes and anterolisthesis.
Abstract: Study design Cross-sectional cohort study of a general population. Objective To investigate "abnormal" lumbar spine magnetic resonance imaging (MRI) findings, and their prevalence and associations with low back pain (LBP). Summary of background data The clinical relevance of various "abnormal" findings in the lumbar spine is unclear. Distinguishing between inevitable age-related findings and degenerative findings with deleterious consequences is a challenge. Methods Lumbar spine MRI was obtained in 412, 40-year-old individuals. Predefined "abnormal" MRI findings were interpreted without any knowledge of patient symptoms. Associations between MRI abnormalities and LBP were calculated using odds ratios. The "overall picture" of each MRI finding was established on the basis of the frequencies, diagnostic values, and the strength and consistency of associations. Results Most "abnormal" MRI findings were found at the lowest lumbar levels. Irregular nucleus shape and reduced disc height were common (>50% of individuals). Relatively common (25% to 50%) were hypointense disc signal, anular tears, high intensity zones, disc protrusions, endplate changes, zygapophyseal joint degeneration, asymmetry, and foraminal stenosis. Nerve root compromise, Modic changes, central spinal stenosis, and anterolisthesis/retrolisthesis were rare ( 4). Significantly positive associations with all LBP variables were seen for hypointense disc signals, reduced disc height, and Modic changes. All disc "abnormalities" except protrusion were moderately associated with LBP during the past year. Conclusion Most degenerative disc "abnormalities" were moderately associated with LBP. The strongest associations were noted for Modic changes and anterolisthesis. Further studies are needed to define clinical relevance.
TL;DR: In primary school-aged children, walking to school is associated with higher levels of overall physical activity compared with those who travel to school by motorized transport.
TL;DR: Heme complexes are removed by a receptor-mediated pathway showing striking similarities to the CD163-mediated haptoglobin-hemoglobin clearance in macrophages, indicating a hitherto unknown role of LRP/CD91 in inflammation.
TL;DR: In this paper, a simulation model of international tourism is presented that fills the gap of analysis of the global changes in tourism demand, and the current pattern of international tourist flows is modelled using 1995 data on departures and arrivals for 207 countries.
Abstract: The literature on tourism and climate change lacks an analysis of the global changes in tourism demand. Here, a simulation model of international tourism is presented that fills that gap. The current pattern of international tourist flows is modelled using 1995 data on departures and arrivals for 207 countries. Using this basic model the impact on arrivals and departures through changes in population, per capita income and climate change are analysed. In the medium to long term, tourism will grow, however, the change from climate change is smaller than from population and income changes.
TL;DR: The male gametocyte has the most distinct proteome, containing many proteins involved in flagellar-based motility and rapid genome replication, and new sex-specific regulatory pathways were defined.
TL;DR: The authors found that Greenlandic consumer acculturation is broadly supportive of the post-assimilationist model, but that acculturative processes in the Danish context lead immigrants to adopt identity positions not entirely consistent with those reported in previous postimilationist consumer research.
Abstract: Data collected among Greenlandic immigrants in Denmark fuel a critical examination of the postassimilationist model of ethnic consumer behavior in a non–North American context. We find that Greenlandic consumer acculturation is broadly supportive of the postassimilationist model. However, acculturative processes in the Danish context lead immigrants to adopt identity positions not entirely consistent with those reported in previous postassimilationist consumer research. Further, we identify transnational consumer culture as an acculturative agent not identified in previous research on consumer ethnicity and question the performative model of culture swapping. Finally, the analysis supports ideas about postassimilationist ethnicity as culture consumed.
TL;DR: The demonstration of an injury-enhanced recruitment of bone marrow-derived cells into the perforant path-denervated dentate gyrus, raises the possibility of using genetically manipulated cells as vectors for lesion-site-specific gene therapy even in minimally injured areas of the central nervous system.
TL;DR: It is shown that a common dynamic interpretation framework, based on rigorous flux expressions incorporating the relevant diffusion and reaction steps, is applicable for a suite of sensors that span a range of time scales.
Abstract: Dynamic metal speciation analysis in aquatic ecosystems is emerging as a powerful basis for development of predictions of bioavailability and reliable risk assessment strategies. A given speciation sensor is characterized by an effective time scale or kinetic window that defines the measurable metal species via their labilities. Here we review the current state of the art for the theory and application of dynamic speciation sensors. We show that a common dynamic interpretation framework, based on rigorous flux expressions incorporating the relevant diffusion and reaction steps, is applicable for a suite of sensors that span a range of time scales. Interpolation from a kinetic spectrum of speciation data is proposed as a practical strategy for addressing questions of bioavailability. Case studies illustrate the practical significance of knowledge on the dynamic features of metal complex species in relation to biouptake, and highlight the limitations of equilibrium-based models.
TL;DR: The synthesized feedback control law is nonlinear and time-dependent and derived from a feedback structure that explicitly uses the general or full integral of the systems zero dynamics to generate a periodic solution and makes it exponentially orbitally stable.
Abstract: We present a constructive tool for generation and orbital stabilization of periodic solutions for underactuated nonlinear systems. Our method can be applied to any mechanical system with a number of independent actuators smaller than the number of degrees of freedom by one. The synthesized feedback control law is nonlinear and time-dependent. It is derived from a feedback structure that explicitly uses the general or full integral of the systems zero dynamics. The control law generates a periodic solution and makes it exponentially orbitally stable.
TL;DR: The gene product of Cfr from Staphylococcus sciuri confers resistance to chloramphenicol, florfenicol and clindamycin in Staphylon spp. and Escherichia coli as mentioned in this paper.
Abstract: Summary
The gene product of cfr from Staphylococcus sciuri confers resistance to chloramphenicol, florfenicol and clindamycin in Staphylococcus spp. and Escherichia coli. Cfr is not similar to any other known chloramphenicol resistance determinant. Comparative investigation of E. coli with and without a plasmid-encoded Cfr showed a decreased drug binding to ribosomes in the presence of Cfr. As chloramphenicol/florfenicol and clindamycin have partly overlapping drug binding sites on the ribosome, the most likely explanation is that Cfr modifies the RNA in the drug binding site. This hypothesis was supported by drug footprinting data that showed both a decreased drug binding and an enhanced reverse transcriptase stop at position 2504, which corresponds to a modification at position A2503 at the drug binding site. A 45 n long RNA fragment containing the appropriate region was isolated and MALDI-TOF mass spectrometry in combination with tandem mass spectrometry showed an additional methylation at position A2503. Moreover, reduced methylation was detected at nucleotide C2498. The results show that Cfr is an RNA methyltransferase that targets nucleotide A2503 and inhibits ribose methylation at nucleotide C2498, thereby causing resistance to chloramphenicol, florfenicol and clindamycin.