Effect of diet and omega-3 fatty acid intervention on asymmetric dimethylarginine

BACKGROUND AND AIM: Impaired vasodilatation has been suggested to be caused by inhibition of nitric oxide generation by the recently described asymmetric dimethylarginine (ADMA). In the present study we wanted to explore whether n-3 polyunsaturated fatty acid (PUFA) supplementation and/or diet intervention have beneficial influence on endothelial function assessed as plasma levels of ADMA and L-arginine. METHODS: A male population (n = 563, age 70 ± 6 yrs) with long-standing hyperlipidemia, characterized as high risk individuals in 1970–72, was included, randomly allocated to receive placebo n-3 PUFA capsules (corn oil) and no dietary advice (control group), dietary advice (Mediterranean type), n-3 PUFA capsules, or dietary advice and n-3 PUFA combined and followed for 3 years. Fasting blood samples were drawn at baseline and the end of the study. RESULTS: Compliance with both intervention regimens were demonstrated by changes in serum fatty acids and by recordings from a food frequency questionnaire. No influence of either regimens on ADMA levels were obtained. However, n-3 PUFA supplementation was accompanied by a significant increase in L-arginine levels, different from the decrease observed in the placebo group (p < 0.05). In individuals with low body mass index (<26 kg/m(2)), the decrease in L-arginine on placebo was strengthened (p = 0.01), and the L-arginine/ADMA ratio was also significantly reduced (p = 0.04). CONCLUSION: In this rather large randomized intervention study, ADMA levels were not influenced by n-3 PUFA supplementation or dietary counselling. n-3 PUFA did, however, counteract the age-related reduction in L-arginine seen on placebo, especially in lean individuals, which might be discussed as an improvement of endothelial function

Treatment completion for latent tuberculosis infection in Norway: a prospective cohort study

Background: Successful treatment of latent tuberculosis infection (LTBI) is essential to reduce tuberculosis (TB) incidence rates in low-burden countries. This study measures treatment completion and determinants of non-completion of LTBI treatment in Norway in 2016. Methods: This prospective cohort study included all individuals notified with LTBI treatment to the Norwegian Surveillance System for Infectious Diseases (MSIS) in 2016. We obtained data from MSIS and from a standardized form that was sent to health care providers at the time of patient notification to MSIS. We determined completion rates. Pearson’s chi squared test was used to study associations between pairs of categorical variables and separate crude and multivariable logistic regression models were used to identify factors associated with treatment completion and adverse drug effects. Results: We obtained information on treatment completion from 719 of the 726 individuals notified for LTBI treatment in 2016. Overall, 91% completed treatment. Treatment completion was highest in the foreign-born group [foreign-born, n = 562 (92%) vs Norwegian-born, n = 115 (85%), p = 0.007]. Treatment completion did not differ significantly between prescribed regimens (p = 0.124). Adverse events were the most common reason for incomplete treatment. We found no significant differences in adverse events when comparing weekly rifapentine (3RPH) with three months daily isoniazid and rifampicin (3RH). However, there were significantly fewer adverse events with 3RPH compared to other regimens (p = 0.037). Age over 35 years was significantly associated with adverse events irrespective of regimen (p = 0.024), whereas immunosuppression was not significantly associated with adverse events after adjusting for other variables (p = 0.306). Treatment under direct observation had a significant effect on treatment completion for foreign-born (multivariate Wald p-value = 0.017), but not for Norwegian-born (multivariate Wald p-value = 0.408) individuals. Conclusions: We report a very high treatment completion rate, especially among individuals from countries with high TB incidence. The follow-up from tuberculosis-coordinators and the frequent use of directly observed treatment probably contributes to this. Few severe adverse events were reported, even with increased age and in individuals that are more susceptible. While these results are promising, issues of cost-effectiveness and targeting treatment to individuals at highest risk of TB are important components of public health impact.publishedVersio

Theoretical and Phenomenological Constraints on Form Factors for Radiative and Semi-Leptonic B-Meson Decays

We study transition form factors for radiative and rare semi-leptonic B-meson decays into light pseudoscalar or vector mesons, combining theoretical constraints and phenomenological information from Lattice QCD, light-cone sum rules, and dispersive bounds. We pay particular attention to form factor parameterisations which are based on the so-called series expansion, and study the related systematic uncertainties on a quantitative level. In this context, we also provide the NLO corrections to the correlation function between two flavour-changing tensor currents, which enters the unitarity constraints for the coefficients in the series expansion.Comment: 52 pages; v2: normalization error in (29ff.) corrected, conclusion about relevance of unitarity bounds modified; form factor fits unaffected; references added; v3: discussion on truncation of series expansion added, matches version to be published in JHEP; v4: corrected typos in Tables 5 and

Detection of multipartite entanglement with two-body correlations

We show how to detect entanglement with criteria built from simple two-body correlation terms. Since many natural Hamiltonians are sums of such correlation terms, our ideas can be used to detect entanglement by energy measurement. Our criteria can straightforwardly be applied for detecting different forms of multipartite entanglement in familiar spin models in thermal equilibrium.Comment: 5 pages including 2 figures, LaTeX; for the proceedings of the DPG spring meeting, Berlin, March 200

Absence of N-terminal acetyltransferase diversification during evolution of eukaryotic organisms

Protein N-terminal acetylation is an ancient and ubiquitous co-translational modification catalyzed by a highly conserved family of N-terminal acetyltransferases (NATs). Prokaryotes have at least 3 NATs, whereas humans have six distinct but highly conserved NATs, suggesting an increase in regulatory complexity of this modification during eukaryotic evolution. Despite this, and against our initial expectations, we determined that NAT diversification did not occur in the eukaryotes, as all six major human NATs were most likely present in the Last Eukaryotic Common Ancestor (LECA). Furthermore, we also observed that some NATs were actually secondarily lost during evolution of major eukaryotic lineages; therefore, the increased complexity of the higher eukaryotic proteome occurred without a concomitant diversification of NAT complexes

Entangled Quantum States of Magnetic Dipoles

Free magnetic moments usually manifest themselves in Curie Laws, where weak external magnetic fields produce magnetizations diverging as the reciprocal 1/T of the temperature. for a variety of materials that do not disply static magnetism, including doped semiconductors and certain rare earth intermetallics, the 1/T law is changed to a power law T^-a with a<1. We report here that a considerably simpler material, namely an insulating magneticsalt can also display such a power law, and show via comparison to specific heat data and numerical simulations that quantum mechanics is crucial for its formation. Two quantum mechanical phenomena are needed, namely level splitting - which affects the spectrum of excited states - and entanglement - where the wavefunction of a system with several degrees of freedom cannot be written as a product of wavefunctions for each degree of freedom. Entanglement effects become visible for remarkably small tunnelling terms, and are turned on well before tunnelling has visible effects on the spectrum. Our work is significant because it illustrates that entanglement is at the very heart of a very simple experimental observation for an insulating quantum spin system.Comment: 17 pages, 4 figure

Saving lives in road traffic—ethical aspects

Aim: This article aims at giving an overview of five ethical problem areas relating to traffic safety, thereby providing a general framework for analysing traffic safety from an ethical perspective and encouraging further discussion concerning problems, policies and technology in this area. Subjects and methods: The problems presented in the article are criminalisation, paternalism, privacy, justice and responsibility, and the reasons for choosing these are the following. First, they are all important areas in moral philosophy. Second, they are fairly general and it should be possible to categorise more specific problems under these headings. Ethical aspects of road traffic have not received the philosophical attention they deserve. Every year, more than 1 million people die globally in traffic accidents, and 20 to 50 million people are injured. Ninety per cent of the road traffic fatalities occur in low- and middle-income countries, where it is a growing problem. Politics, economics, culture and technology affect the number of fatalities and injuries, and the measures used to combat deaths in traffic as well as the role of road traffic should be ethically scrutinised. The topics are analysed and discussed from a moral-philosophical perspective, and the discussion includes both theory and applications. Results and conclusion: The author concludes with some thoughts on how the ethical discussion can be included in the public debate on how to save lives in road traffic. People in industrialised societies are so used to road traffic that it is almost seen as part of nature. Consequently, we do not acknowledge that we can introduce change and that we can affect the role we have given road traffic and cars. By acknowledging the ethical aspects of road traffic and illuminating the way the choices society makes are ethically charged, it becomes clear that there are alternative ways to design the road traffic system. The most important general conclusion is that discussion concerning these alternative ways of designing the system should be encouraged

Modification of Collagen by 3-Deoxyglucosone Alters Wound Healing through Differential Regulation of p38 MAP Kinase

Background: Wound healing is a highly dynamic process that requires signaling from the extracellular matrix to the fibroblasts for migration and proliferation, and closure of the wound. This rate of wound closure is impaired in diabetes, which may be due to the increased levels of the precursor for advanced glycation end products, 3-deoxyglucosone (3DG). Previous studies suggest a differential role for p38 mitogen-activated kinase (MAPK) during wound healing; whereby, p38 MAPK acts as a growth kinase during normal wound healing, but acts as a stress kinase during diabetic wound repair. Therefore, we investigated the signaling cross-talk by which p38 MAPK mediates wound healing in fibroblasts cultured on native collagen and 3DG-collagen. Methodology/Principal Findings: Using human dermal fibroblasts cultured on 3DG-collagen as a model of diabetic wounds, we demonstrated that p38 MAPK can promote either cell growth or cell death, and this was dependent on the activation of AKT and ERK1/2. Wound closure on native collagen was dependent on p38 MAPK phosphorylation of AKT and ERK1/2. Furthermore, proliferation and collagen production in fibroblasts cultured on native collagen was dependent on p38 MAPK regulation of AKT and ERK1/2. In contrast, 3DG-collagen decreased fibroblast migration, proliferation, and collagen expression through ERK1/2 and AKT downregulation via p38 MAPK. Conclusions/Significance: Taken together, the present study shows that p38 MAPK is a key signaling molecule that plays

Whole-genome phylogenies of the family Bacillaceae and expansion of the sigma factor gene family in the Bacillus cereus species-group

<p>Abstract</p> <p>Background</p> <p>The <it>Bacillus cereus </it><it>sensu lato </it>group consists of six species (<it>B. anthracis</it>, <it>B. cereus</it>, <it>B. mycoides</it>, <it>B. pseudomycoides</it>, <it>B. thuringiensis</it>, and <it>B. weihenstephanensis</it>). While classical microbial taxonomy proposed these organisms as distinct species, newer molecular phylogenies and comparative genome sequencing suggests that these organisms should be classified as a single species (thus, we will refer to these organisms collectively as the <it>Bc </it>species-group). How do we account for the underlying similarity of these phenotypically diverse microbes? It has been established for some time that the most rapidly evolving and evolutionarily flexible portions of the bacterial genome are regulatory sequences and transcriptional networks. Other studies have suggested that the sigma factor gene family of these organisms has diverged and expanded significantly relative to their ancestors; sigma factors are those portions of the bacterial transcriptional apparatus that control RNA polymerase recognition for promoter selection. Thus, examining sigma factor divergence in these organisms would concurrently examine both regulatory sequences and transcriptional networks important for divergence. We began this examination by comparison to the sigma factor gene set of <it>B. subtilis</it>.</p> <p>Results</p> <p>Phylogenetic analysis of the <it>Bc </it>species-group utilizing 157 single-copy genes of the family <it>Bacillaceae </it>suggests that several taxonomic revisions of the genus <it>Bacillus </it>should be considered. Within the <it>Bc </it>species-group there is little indication that the currently recognized species form related sub-groupings, suggesting that they are members of the same species. The sigma factor gene family encoded by the <it>Bc </it>species-group appears to be the result of a dynamic gene-duplication and gene-loss process that in previous analyses underestimated the true heterogeneity of the sigma factor content in the <it>Bc </it>species-group.</p> <p>Conclusions</p> <p>Expansion of the sigma factor gene family appears to have preferentially occurred within the extracytoplasmic function (ECF) sigma factor genes, while the primary alternative (PA) sigma factor genes are, in general, highly conserved with those found in <it>B. subtilis</it>. Divergence of the sigma-controlled transcriptional regulons among various members of the <it>Bc </it>species-group likely has a major role in explaining the diversity of phenotypic characteristics seen in members of the <it>Bc </it>species-group.</p

Dynamics-function relationship in the catalytic domains of N-terminal acetyltransferases

N-terminal acetyltransferases (NATs) belong to the superfamily of acetyltransferases. They are enzymes catalysing the transfer of an acetyl group from acetyl coenzyme A to the N-terminus of polypeptide chains. N-terminal acetylation is one of the most common protein modifications. To date, not much is known on the molecular basis for the exclusive substrate specificity of NATs. All NATs share a common fold called GNAT. A characteristic of NATs is the β6β7 hairpin loop covering the active site and forming with the α1α2 loop a narrow tunnel surrounding the catalytic site in which cofactor and polypeptide meet and exchange an acetyl group. We investigated the dynamics-function relationships of all available structures of NATs covering the three domains of Life. Using an elastic network model and normal mode analysis, we found a common dynamics pattern conserved through the GNAT fold; a rigid V-shaped groove formed by the β4 and β5 strands and splitting the fold in two dynamical subdomains. Loops α1α2, β3β4 and β6β7 all show clear displacements in the low frequency normal modes. We characterized the mobility of the loops and show that even limited conformational changes of the loops along the low-frequency modes are able to significantly change the size and shape of the ligand binding sites. Based on the fact that these movements are present in most low-frequency modes, and common to all NATs, we suggest that the α1α2 and β6β7 loops may regulate ligand uptake and the release of the acetylated polypeptide.publishedVersio