scispace - formally typeset
Search or ask a question

Showing papers by "University of Southern Denmark published in 2006"


Journal ArticleDOI
03 Nov 2006-Cell
TL;DR: A general mass spectrometric technology is developed and applied for identification and quantitation of phosphorylation sites as a function of stimulus, time, and subcellular location to provide a missing link in a global, integrative view of cellular regulation.

3,404 citations


Journal ArticleDOI
TL;DR: Assessment of associations of objectively measured physical activity with clustering of cardiovascular disease risk factors in children from Denmark, Estonia, and Portugal found levels should be higher than the current international guidelines of at at least 1 h per day of physical activity of at least moderate intensity.

1,475 citations


Journal ArticleDOI
20 Jan 2006-Science
TL;DR: The sequence and the structure of DNA methyltransferase-2 (DnMT2) bear close affinities to authentic DNA cytosine methyltransferases, and human DNMT2 protein restored methylation in vitro to tRNAAsp from Dnmt2-deficient strains of mouse, Arabidopsis thaliana, and Drosophila melanogaster in a manner that was dependent on preexisting patterns of modified nucleosides.
Abstract: The sequence and the structure of DNA methyltransferase-2 (Dnmt2) bear close affinities to authentic DNA cytosine methyltransferases. A combined genetic and biochemical approach revealed that human DNMT2 did not methylate DNA but instead methylated a small RNA; mass spectrometry showed that this RNA is aspartic acid transfer RNA (tRNA(Asp)) and that DNMT2 specifically methylated cytosine 38 in the anticodon loop. The function of DNMT2 is highly conserved, and human DNMT2 protein restored methylation in vitro to tRNA(Asp) from Dnmt2-deficient strains of mouse, Arabidopsis thaliana, and Drosophila melanogaster in a manner that was dependent on preexisting patterns of modified nucleosides. Indirect sequence recognition is also a feature of eukaryotic DNA methyltransferases, which may have arisen from a Dnmt2-like RNA methyltransferase.

1,059 citations


Journal ArticleDOI
TL;DR: The prevalence of neck pain in the world population is determined and generally women have more NP than men and Scandinavian countries report higher mean estimates than the rest of Europe and Asia.
Abstract: The objective of this study was to determine the prevalence of neck pain (NP) in the world population and to identify areas of methodological variation between studies. A systematic search was conducted in five databases (MEDLINE, EMBASE, CINAHL, OSH-ROM, and PsycINFO), followed by a screening of reference lists of relevant papers. Included papers were extracted for information and each paper was given a quality score. Mean prevalence estimates were calculated for six prevalence periods (point, week, month, 6 months, year, and lifetime), and considered separately for age, gender, quality score, response rate, sample size, anatomical definition, geography, and publication year. Fifty-six papers were included. The six most commonly reported types of prevalence were point, week, month, 6 months, year, and lifetime. Except for lifetime prevalence, women reported more NP than men. For 1-year prevalence, Scandinavian countries reported more NP than the rest of Europe and Asia. Prevalence estimates were not affected by age, quality score, sample size, response rate, and different anatomical definitions of NP. NP is a common symptom in the population. As expected, the prevalence increases with longer prevalence periods and generally women have more NP than men. At least for 1-year prevalence Scandinavian countries report higher mean estimates than the rest of Europe and Asia. The quality of studies varies greatly but is not correlated with the prevalence estimates. Design varies considerably and standardisation is needed in future studies.

994 citations


Proceedings ArticleDOI
22 Apr 2006
TL;DR: A framework that focuses on the interweaving of the material/physical and the social, contributes to understanding the (social) user experience of tangible interaction, and provides concepts and perspectives for considering the social aspects ofangible interaction is introduced.
Abstract: Our current understanding of human interaction with hybrid or augmented environments is very limited. Here we focus on 'tangible interaction', denoting systems that rely on embodied interaction, tangible manipulation, physical representation of data, and embeddedness in real space. This synthesis of prior 'tangible' definitions enables us to address a larger design space and to integrate approaches from different disciplines. We introduce a framework that focuses on the interweaving of the material/physical and the social, contributes to understanding the (social) user experience of tangible interaction, and provides concepts and perspectives for considering the social aspects of tangible interaction. This understanding lays the ground for evolving knowledge on collaboration-sensitive tangible interaction design. Lastly, we analyze three case studies, using the framework, thereby illustrating the concepts and demonstrating their utility as analytical tools.

978 citations


Journal ArticleDOI
12 Jan 2006-Nature
TL;DR: It is shown that TRAF3 is essential for the induction of type I interferons (IFN) and the anti-inflammatory cytokine interleukin-10 (IL-10), but is dispensable for expression of pro- inflammatory cytokines, owing to defective IL-10 production.
Abstract: Toll-like receptors (TLRs) are activated by pathogen-associated molecular patterns to induce innate immune responses and production of pro-inflammatory cytokines, interferons and anti-inflammatory cytokines. TLRs activate downstream effectors through adaptors that contain Toll/interleukin-1 receptor (TIR) domains, but the mechanisms accounting for diversification of TLR effector functions are unclear. To dissect biochemically TLR signalling, we established a system for isolating signalling complexes assembled by dimerized adaptors. Using MyD88 as a prototypical adaptor, we identified TNF receptor-associated factor 3 (TRAF3) as a new component of TIR signalling complexes that is recruited along with TRAF6. Using myeloid cells from TRAF3- and TRAF6-deficient mice, we show that TRAF3 is essential for the induction of type I interferons (IFN) and the anti-inflammatory cytokine interleukin-10 (IL-10), but is dispensable for expression of pro-inflammatory cytokines. In fact, TRAF3-deficient cells overproduce pro-inflammatory cytokines owing to defective IL-10 production. Despite their structural similarity, the functions of TRAF3 and TRAF6 are largely distinct. TRAF3 is also recruited to the adaptor TRIF (Toll/IL-1 receptor domain-containing adaptor-inducing IFN-beta) and is required for marshalling the protein kinase TBK1 (also called NAK) into TIR signalling complexes, thereby explaining its unique role in activation of the IFN response.

935 citations


Journal ArticleDOI
TL;DR: In this article, the authors consider how innovators benefit from value appropriation and creation, and they provide an integrative guide that explains how firms should manage their position along the value chain to capture returns from innovation, thus extending and qualifying Teece's original predictions and prescriptions.
Abstract: Extending Teece's landmark 1986 article, we consider how innovators benefit from value appropriation and creation. We elaborate on value appropriation, first by pointing out the importance of "industry architectures", i.e. sector-wide templates that circumscribe the division of labor; and second, by treating complementarity and factor mobility as distinctive components of cospecialization. This allows us to qualify Teece's prediction, by positing that firms can create an "architectural advantage" in terms of high levels of value appropriation without the need to engage in vertical integration. Such architectural advantage comes about when firms can enhance both complementarity and mobility in parts of the value chain where they are not active. We then elaborate on value creation by indicating how actors can benefit from investing in assets that appreciate because of innovation, which suggests that firms can benefit from encouraging imitation while investing in complementary assets. We also consider how investment in complementary assets changes the scope of the firm and thereby the development of capabilities that support future innovation. Finally, we provide an integrative guide that explains how firms should manage their position along the value chain to capture returns from innovation, thus extending and qualifying Teece's (1986) original predictions and prescriptions.

705 citations


Journal ArticleDOI
TL;DR: TV viewing and PA may be separate entities and differently associated with adiposity and metabolic risk, whereas PA is associated with individual and clustered metabolic-risk indicators independently of obesity.
Abstract: Background TV viewing has been linked to metabolic-risk factors in youth. However, it is unclear whether this association is independent of physical activity (PA) and obesity. Methods and Findings We did a population-based, cross-sectional study in 9- to 10-y-old and 15- to 16-y-old boys and girls from three regions in Europe (n = 1,921). We examined the independent associations between TV viewing, PA measured by accelerometry, and metabolic-risk factors (body fatness, blood pressure, fasting triglycerides, inverted high-density lipoprotein (HDL) cholesterol, glucose, and insulin levels). Clustered metabolic risk was expressed as a continuously distributed score calculated as the average of the standardized values of the six subcomponents. There was a positive association between TV viewing and adiposity (p = 0.021). However, after adjustment for PA, gender, age group, study location, sexual maturity, smoking status, birth weight, and parental socio-economic status, the association of TV viewing with clustered metabolic risk was no longer significant (p = 0.053). PA was independently and inversely associated with systolic and diastolic blood pressure, fasting glucose, insulin (all p < 0.01), and triglycerides (p = 0.02). PA was also significantly and inversely associated with the clustered risk score (p < 0.0001), independently of obesity and other confounding factors. Conclusions TV viewing and PA may be separate entities and differently associated with adiposity and metabolic risk. The association between TV viewing and clustered metabolic risk is mediated by adiposity, whereas PA is associated with individual and clustered metabolic-risk indicators independently of obesity. Thus, preventive action against metabolic risk in children may need to target TV viewing and PA separately.

663 citations


Journal ArticleDOI
TL;DR: The findings show that a mammalian sirtuin directly controls the activity of a metabolic enzyme by means of reversible lysine acetylation, and highlights the conservation of a metabolism regulatory pathway from bacteria to humans.
Abstract: We report that human acetyl-CoA synthetase 2 (AceCS2) is a mitochondrial matrix protein. AceCS2 is reversibly acetylated at Lys-642 in the active site of the enzyme. The mitochondrial sirtuin SIRT3 interacts with AceCS2 and deacetylates Lys-642 both in vitro and in vivo. Deacetylation of AceCS2 by SIRT3 activates the acetyl-CoA synthetase activity of AceCS2. This report identifies the first acetylated substrate protein of SIRT3. Our findings show that a mammalian sirtuin directly controls the activity of a metabolic enzyme by means of reversible lysine acetylation. Because the activity of a bacterial ortholog of AceCS2, called ACS, is controlled via deacetylation by a bacterial sirtuin protein, our observation highlights the conservation of a metabolic regulatory pathway from bacteria to humans.

658 citations


Journal ArticleDOI
TL;DR: The analysis provides a high-confidence set of proteins present in human urinary proteome and provides a useful reference for comparing datasets obtained using different methodologies and may prove useful in biomarker discovery in the future.
Abstract: Urine is a desirable material for the diagnosis and classification of diseases because of the convenience of its collection in large amounts; however, all of the urinary proteome catalogs currently being generated have limitations in their depth and confidence of identification. Our laboratory has developed methods for the in-depth characterization of body fluids; these involve a linear ion trap-Fourier transform (LTQ-FT) and a linear ion trap-orbitrap (LTQ-Orbitrap) mass spectrometer. Here we applied these methods to the analysis of the human urinary proteome. We employed one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis and reverse phase high-performance liquid chromatography for protein separation and fractionation. Fractionated proteins were digested in-gel or in-solution, and digests were analyzed with the LTQ-FT and LTQ-Orbitrap at parts per million accuracy and with two consecutive stages of mass spectrometric fragmentation. We identified 1543 proteins in urine obtained from ten healthy donors, while essentially eliminating false-positive identifications. Surprisingly, nearly half of the annotated proteins were membrane proteins according to Gene Ontology (GO) analysis. Furthermore, extracellular, lysosomal, and plasma membrane proteins were enriched in the urine compared with all GO entries. Plasma membrane proteins are probably present in urine by secretion in exosomes. Our analysis provides a high-confidence set of proteins present in human urinary proteome and provides a useful reference for comparing datasets obtained using different methodologies. The urinary proteome is unexpectedly complex and may prove useful in biomarker discovery in the future.

647 citations


Journal ArticleDOI
TL;DR: In this article, the authors consider how innovators benefit from value appropriation and creation, and they provide an integrative guide that explains how firms should manage their position along the value chain to capture returns from innovation.

Journal ArticleDOI
TL;DR: The findings described in this study represent the first report of a gene conferring transferable resistance to pleuromutilins and oxazolidinones and the phenotype is named PhLOPSA for resistance to the following drug classes.
Abstract: A novel multidrug resistance phenotype mediated by the Cfr rRNA methyltransferase is observed in Staphylococcus aureus and Escherichia coli. The cfr gene has previously been identified as a phenicol and lincosamide resistance gene on plasmids isolated from Staphylococcus spp. of animal origin and recently shown to encode a methyltransferase that modifies 23S rRNA at A2503. Antimicrobial susceptibility testing shows that S. aureus and E. coli strains expressing the cfr gene exhibit elevated MICs to a number of chemically unrelated drugs. The phenotype is named PhLOPSA for resistance to the following drug classes: Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A antibiotics. Each of these five drug classes contains important antimicrobial agents that are currently used in human and/or veterinary medicine. We find that binding of the PhLOPSA drugs, which bind to overlapping sites at the peptidyl transferase center that abut nucleotide A2503, is perturbed upon Cfr-mediated methylation. Decreased drug binding to Cfr-methylated ribosomes has been confirmed by footprinting analysis. No other rRNA methyltransferase is known to confer resistance to five chemically distinct classes of antimicrobials. In addition, the findings described in this study represent the first report of a gene conferring transferable resistance to pleuromutilins and oxazolidinones.

Journal ArticleDOI
TL;DR: A protocol for selective phosphopeptide enrichment using titanium dioxide (TiO2) chromatography is described, well suited for the characterization of phosphoproteins from both in vitro and in vivo studies in combination with mass spectrometry (MS).
Abstract: The characterization of phosphorylated proteins is a challenging analytical task since many of the proteins targeted for phosphorylation are low in abundance and phosphorylation is typically substoichiometric. Highly efficient enrichment procedures are therefore required. Here we describe a protocol for selective phosphopeptide enrichment using titanium dioxide (TiO2) chromatography. The selectivity toward phosphopeptides is obtained by loading the sample in a 2,5-dihydroxybenzoic acid (DHB) or phthalic acid solution containing acetonitrile and trifluoroacetic acid (TFA) onto a TiO2 micro-column. Although phosphopeptide enrichment can be achieved by using TFA and acetonitrile alone, the selectivity is dramatically enhanced by adding DHB or phthalic acid since these compounds, in conjunction with the low pH caused by TFA, prevent binding of nonphosphorylated peptides to TiO2. Using an alkaline solution (pH > or = 10.5) both monophosphorylated and multiphosphorylated peptides are eluted from the TiO2 beads. This highly efficient method for purification of phosphopeptides is well suited for the characterization of phosphoproteins from both in vitro and in vivo studies in combination with mass spectrometry (MS). It is a very easy and fast method. The entire protocol requires less than 15 min per sample if the buffers have been prepared in advance (not including lyophilization).

Journal ArticleDOI
07 Apr 2006-Cell
TL;DR: This analysis ties biochemistry, cell biology, and genomics into a common framework for organelle analysis and identifies networks of coexpressed genes, cis-regulatory motifs, and putative transcriptional regulators involved in organelle biogenesis.

Journal ArticleDOI
01 Nov 2006-Pain
TL;DR: It is remarkable that opioid treatment of long‐term/chronic non‐cancer pain does not seem to fulfil any of the key outcome opioid treatment goals: pain relief, improved quality of life and improved functional capacity.
Abstract: The aim of the study was epidemiologically to evaluate the long-term effects of opioids on pain relief, quality of life and functional capacity in long-term/chronic non-cancer pain. The study was based on data from the 2000 Danish Health and Morbidity Survey. As part of a representative National random sample of 16,684 individuals (>16 years of age), 10,066 took part in an interview and completed a self-administered questionnaire. Cancer patients were excluded. The interview and the self-administered questionnaire included questions on chronic/long-lasting pain (>6 months), health-related quality of life (SF-36), use of the health care system, functional capabilities, satisfaction with medical pain treatment and regular or continuous use of medications. Participants reporting pain were divided into opioid and non-opioid users. The analyses were adjusted for age, gender, concomitant use of anxiolytics and antidepressants and pain intensity. Pain relief, quality of life and functional capacity among opioid users were compared with non-opioid users. Opioid usage was significantly associated with reporting of moderate/severe or very severe pain, poor self-rated health, not being engaged in employment, higher use of the health care system, and a negative influence on quality of life as registered in all items in SF-36. Because of the cross-sectional nature causative relationships cannot be ascertained. However, it is remarkable that opioid treatment of long-term/chronic non-cancer pain does not seem to fulfil any of the key outcome opioid treatment goals: pain relief, improved quality of life and improved functional capacity.

Journal ArticleDOI
TL;DR: Combining state-of-the-art technologies in molecular cell biology, protein mass spectrometry and bioinformatics, it is now feasible to discover and study the structural and functional roles of distinct protein post-translational modifications.
Abstract: Post-translational modifications define the functional and structural plasticity of proteins in archaea, prokaryotes and eukaryotes. Multi-site protein modification modulates protein activity and macromolecular interactions and is involved in a range of fundamental molecular processes. Combining state-of-the-art technologies in molecular cell biology, protein mass spectrometry and bioinformatics, it is now feasible to discover and study the structural and functional roles of distinct protein post-translational modifications.

Journal ArticleDOI
TL;DR: Stable isotope labeling with amino acids in cell culture (SILAC) method is demonstrated to compare the secreted proteins (secretome) from pancreatic cancer-derived cells with that from non-neoplastic pancreatic ductal cells, confirming the validity of this approach.

Journal ArticleDOI
TL;DR: Large-scale linkage studies of long-lived families, longitudinal candidate-gene association studies and the development of analytical methods provide the potential for future progress in human studies of longevity.
Abstract: Twin studies show that genetic differences account for about a quarter of the variance in adult human lifespan. Common polymorphisms that have a modest effect on lifespan have been identified in one gene, APOE, providing hope that other genetic determinants can be uncovered. However, although variants with substantial beneficial effects have been proposed to exist and several candidates have been put forward, their effects have yet to be confirmed. Human studies of longevity face numerous theoretical and logistical challenges, as the determinants of lifespan are extraordinarily complex. However, large-scale linkage studies of long-lived families, longitudinal candidate-gene association studies and the development of analytical methods provide the potential for future progress.

Journal ArticleDOI
TL;DR: The effects on brain function associated with prenatal methylmercury exposure appear to be multi-focal and permanent, supported by independent assessment of neurophysiological outcomes.

Journal ArticleDOI
TL;DR: In this paper, the authors present an analysis of global youth cultural consumption based on a multisited empirical study of young consumers in Denmark and Greenland, treating youth culture as a market ideology by tracing the emergence of youth culture in relation to marketing and how the ideology has glocalized.
Abstract: In this article we present an analysis of global youth cultural consumption based on a multisited empirical study of young consumers in Denmark and Greenland. We treat youth culture as a market ideology by tracing the emergence of youth culture in relation to marketing and how the ideology has glocalized. This transnational market ideology is manifested in the glocalization of three structures of common difference that organize our data: identity, center‐periphery, and reference to youth cultural consumption styles. Our study goes beyond accounts of global homogenization and local appropriation by showing the glocal structural commonalities in diverse manifestations of youth culture.

Journal ArticleDOI
15 Feb 2006-Spine
TL;DR: In this paper, the authors found that low back pain in childhood may have important consequences for future low-back pain in adulthood, and they also demonstrated a dose-response association: the more days with low back symptoms at baseline, the higher the risk of future low back problems.
Abstract: Study design Prospective study with 8-year follow-up. Objective To describe the evolution of low back pain from adolescence into adulthood. Summary of background data High prevalence rates of low back pain among children and adolescents have been demonstrated in several studies, and it has been theorized that low back pain in childhood may have important consequences for future low back pain. It is important to understand the nature of such a link if effective preventive programs are to be established. Methods Almost 10,000 Danish twins born between 1972 and 1982 were surveyed by means of postal questionnaires in 1994 and again in 2002. The questionnaires dealt with various aspects of general health, including the prevalence of low back pain, classified according to number of days affected (0, 1-7, 8-30, >30). Results Low back pain in adolescence was found to be a significant risk factor for low back pain in adulthood with odds ratios as high as four. We also demonstrated a dose-response association: the more days with low back pain at baseline, the higher the risk of future low back pain. Twenty-six percent of those with low back pain for more than 30 days during the baseline year also had more than 30 days with low back pain during the follow-up year. This was true for only 9% of the rest of the sample. Conclusions Our study clearly demonstrates correlations between low back pain in childhood/adolescence and low back pain in adulthood. This should lead to a change in focus from the adult to the young population in relation to research, prevention, and treatment.

Journal ArticleDOI
05 Oct 2006-BMJ
TL;DR: During the study period, exposure to combined antithrombotic regimens increased by 425% in the background population and is associated with high incidence of gastrointestinal bleeding.
Abstract: Objectives To assess the risk of serious upper gastrointestinal bleeding associated with the newer antithrombotic agents used alone or in combination with other antithrombotic drugs; to describe the trends in use of antithrombotic drugs in the background population. Design Population based case-control study. Setting Funen County, Denmark (population 470 000). Subjects 1443 cases of serious upper gastrointestinal bleeding identified during 2000-4; 57 720 age and sex matched controls. Main outcome measure Exposure to low dose aspirin, clopidogrel, dipyridamole, vitamin K antagonists, and combined antithrombotic treatment. Results Adjusted odds ratios associating drug use with upper gastrointestinal bleeding were 1.8 (95% confidence interval 1.5 to 2.1) for low dose aspirin, 1.1 (0.6 to 2.1) for clopidogrel, 1.9 (1.3 to 2.8) for dipyridamole, and 1.8 (1.3 to 2.4) for vitamin K antagonists. Corresponding figures for combined use were 7.4 (3.5 to 15) for clopidogrel and aspirin, 5.3 (2.9 to 9.5) for vitamin K antagonists and aspirin, and 2.3 (1.7 to 3.3) for dipyridamole and aspirin. Other combinations were used too infrequently to allow estimation. The number of treatment years needed to produce one excess case varied from 124 for the clopidogrel-aspirin combination to 8800 for clopidogrel alone. During the study period, exposure to combined antithrombotic regimens increased by 425% in the background population. Conclusion Antithrombotic treatment is becoming increasingly aggressive. Combined antithrombotic treatment confers particular risk and is associated with high incidence of gastrointestinal bleeding.

Journal ArticleDOI
TL;DR: It is found that genetic influences on lifespan are minimal prior to age 60 but increase thereafter and these findings provide a support for the search for genes affecting longevity in humans, especially at advanced ages.
Abstract: There is an intense search for longevity genes in both animal models and humans. Human family studies have indicated that a modest amount of the overall variation in adult lifespan (approximately 20-30%) is accounted for by genetic factors. But it is not known if genetic factors become increasingly important for survival at the oldest ages. We study the genetic influence on human lifespan and how it varies with age using the almost extinct cohorts of Danish, Finnish and Swedish twins born between 1870 and 1910 comprising 20,502 individuals followed until 2003-2004. We first estimate mean lifespan of twins by lifespan of co-twin and then turn to the relative recurrence risk of surviving to a given age. Mean lifespan for male monozygotic (MZ) twins increases 0.39 [95% CI (0.28, 0.50)] years for every year his co-twin survives past age 60 years. This rate is significantly greater than the rate of 0.21 (0.11, 0.30) for dizygotic (DZ) males. Females and males have similar rates and these are negligible before age 60 for both MZ and DZ pairs. We moreover find that having a co-twin surviving to old ages substantially and significantly increases the chance of reaching the same old age and this chance is higher for MZ than for DZ twins. The relative recurrence risk of reaching age 92 is 4.8 (2.2, 7.5) for MZ males, which is significantly greater than the 1.8 (0.10, 3.4) for DZ males. The patterns for females and males are very similar, but with a shift of the female pattern with age that corresponds to the better female survival. Similar results arise when considering only those Nordic twins that survived past 75 years of age. The present large population based study shows genetic influence on human lifespan. While the estimated overall strength of genetic influence is compatible with previous studies, we find that genetic influences on lifespan are minimal prior to age 60 but increase thereafter. These findings provide a support for the search for genes affecting longevity in humans, especially at advanced ages.

Journal ArticleDOI
TL;DR: RMQ is suitable for measuring change in LBP only patients and both ODI and RMQ are suitable for leg pain patients irrespectively of patient entry point, which is not affected by baseline score when patients quantified an important improvement.
Abstract: Background The choice of an evaluative instrument has been hampered by the lack of head-to-head comparisons of responsiveness and the minimal clinically important difference (MCID) in subpopulations of low back pain (LBP). The objective of this study was to concurrently compare responsiveness and MCID for commonly used pain scales and functional instruments in four subpopulations of LBP patients.

Journal ArticleDOI
TL;DR: In this paper, the authors present and estimate a model of competition in a two-sided market: the market for magazine readership and advertising, and they find evidence that magazines have properties of twosided markets, consistent with the perception that prices for readers are "subsidized" and that magazines make all their money from advertisers.

Journal ArticleDOI
TL;DR: It is calculated, consistent with the carbon isotope record and other considerations of the carbon cycle, that marine rates of primary production at this time were probably an order of magnitude (or more) less than today.
Abstract: Before the advent of oxygenic photosynthesis, the biosphere was driven by anaerobic metabolisms. We catalogue and quantify the source strengths of the most probable electron donors and electron acceptors that would have been available to fuel early-Earth ecosystems. The most active ecosystems were probably driven by the cycling of H 2 and Fe 2+ through primary production conducted by anoxygenic phototrophs. Interesting and dynamic ecosystems would have also been driven by the microbial cycling of sulphur and nitrogen species, but their activity levels were probably not so great. Despite the diversity of potential early ecosystems, rates of primary production in the early-Earth anaerobic biosphere were probably well below those rates observed in the marine environment. We shift our attention to the Earth environment at 3.8 Gyr ago, where the earliest marine sediments are preserved. We calculate, consistent with the carbon isotope record and other considerations of the carbon cycle, that marine rates of primary production at this time were probably an order of magnitude (or more) less than today. We conclude that the flux of reduced species to the Earth surface at this time may have been sufficient to drive anaerobic ecosystems of sufficient activity to be consistent with the carbon isotope record. Conversely, an ecosystem based on oxygenic photosynthesis was also possible with complete removal of the oxygen by reaction with reduced species from the mantle.

Journal ArticleDOI
TL;DR: The methodological aspects of the aforementioned experimental approaches, particularly stressing the information obtained by the use of UV excited fluorescent probes using two-photon excitation fluorescence microscopy, are discussed.

Journal ArticleDOI
TL;DR: This high-confidence characterization of seminal plasma content provides an inventory of proteins with potential roles in fertilization and should be useful for studies of fertilization, male infertility, and prostatic and testicular cancers.
Abstract: Background: The development of mass spectrometric (MS) techniques now allows the investigation of very complex protein mixtures ranging from subcellular structures to tissues. Body fluids are also popular targets of proteomic analysis because of their potential for biomarker discovery. Seminal plasma has not yet received much attention from the proteomics community but its characterization could provide a future reference for virtually all studies involving human sperm. The fluid is essential for the survival of spermatozoa and their successful journey through the female reproductive tract. Results: Here we report the high-confidence identification of 923 proteins in seminal fluid from a single individual. Fourier transform MS enabled parts per million mass accuracy, and two consecutive stages of MS fragmentation allowed confident identification of proteins even by single peptides. Analysis with GoMiner annotated two-thirds of the seminal fluid proteome and revealed a large number of extracellular proteins including many proteases. Other proteins originated from male accessory glands and have important roles in spermatozoan survival. Conclusion: This high-confidence characterization of seminal plasma content provides an inventory of proteins with potential roles in fertilization. When combined with quantitative proteomics methodologies, it should be useful for studies of fertilization, male infertility, and prostatic and testicular cancers.

Journal ArticleDOI
TL;DR: There exists no alternative to the core Darwinian principles of variation, selection and inheritance to explain the evolution of complex evolving population systems.
Abstract: Complex evolving systems, consisting of populations of varied and replicating entities are found in both nature and human society. There exists no alternative to the core Darwinian principles of variation, selection and inheritance to explain the evolution of such systems. Neither the actual existence of human intentionality nor the hypothetical possibility of Lamarckian acquired character inheritance offers a barrier to the use of Darwinian principles. On the contrary, Darwinism is always required to complete the explanation. However, while Darwinian principles are always necessary to explain complex evolving population systems they are never sufficient on their own.

Journal ArticleDOI
TL;DR: Incubations with (15)N labelled nitrate showed that anammox occurred in the suboxic water layer at 100-110 m water depth, providing the first direct evidence for the anamm ox process (anaerobic ammonium oxidation) in a lacustrine system, Lake Tanganyika, the second largest lake in the world.
Abstract: Here we provide the first direct evidence for the anammox process (anaerobic ammonium oxidation) in a lacustrine system, Lake Tanganyika, the second largest lake in the world. Incubations with (15)N labelled nitrate showed that anammox occurred in the suboxic water layer at 100-110 m water depth. Anammox rates up to 10 nM N(2) h(-1) are comparable to those reported for the marine water column. Up to approximately 13% of produced N(2) could be attributed to the anammox process whereas the remainder was related to denitrification. Typical lipid biomarkers characteristic of anammox bacteria were found in filtered water from the depths where anammox occurred, thus supporting the presence of anammox bacteria. Further evidence is provided by fluorescence in situ hybridization (FISH), revealing up to 13 000 anammox bacteria cells per ml or 1.4% of all DAPI (4'-6-Diamidino-2-phenylindole)-stained cells. Phylogenetic analyses of partial 16S rRNA genes indicated the presence of sequences most closely related to the known anammox bacterium Candidatus "Scalindua brodae" (95.7% similarity). Using the incubation results, a total loss of 0.2 Tg N(2) per year linked to anammox was estimated for the Northern basin of Lake Tanganyika.