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Depression is a severe and debilitating mental disorder diagnosed by evaluation of affective, cognitive and physical depression symptoms. Severity of these symptoms strongly impacts individual’s quality of life and is influenced by a combination of genetic and environmental factors. One of the molecular mechanisms allowing for an interplay between these factors is DNA methylation, an epigenetic modification playing a pivotal role in regulation of brain functioning across lifespan. The aim of this study was to investigate if there are DNA methylation signatures associated with depression symptomatology in order to identify molecular mechanisms contributing to pathophysiology of depression. We performed an epigenome-wide association study (EWAS) of continuous depression symptomatology score measured in a cohort of 724 monozygotic Danish twins (346 males, 378 females). Through EWAS analyses adjusted for sex, age, flow-cytometry based blood cell composition, and twin relatedness structure in the data we identified depression symptomatology score to be associated with blood DNA methylation levels in promoter regions of neuropsin (KLK8, p-value = 4.7 × 10−7) and DAZ associated protein 2 (DAZAP2, p-value = 3.13 × 10−8) genes. Other top associated probes were located in gene bodies of MAD1L1 (p-value = 5.16 × 10−6), SLC29A2 (p-value = 6.15 × 10−6) and AKT1 (p-value = 4.47 × 10−6), all genes associated before with development of depression. Additionally, the following three measures (a) DNAmAge (calculated with Horvath and Hannum epigenetic clock estimators) adjusted for chronological age, (b) difference between DNAmAge and chronological age, and (c) DNAmAge acceleration were not associated with depression symptomatology score in our cohort. In conclusion, our data suggests that depression symptomatology score is associated with DNA methylation levels of genes implicated in response to stress, depressive-like behaviors, and recurrent depression in patients, but not with global DNA methylation changes across the genome.

Mutations in the epigenetic modifier TET2 are frequent in myeloid malignancies and clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). Here, we investigate associations between TET2 mutations and DNA methylation in whole blood in 305 elderly twins, 15 patients with CCUS and 18 healthy controls. We find that TET2 mutations are associated with DNA hypermethylation at enhancer sites in whole blood in CHIP and in both granulocytes and mononuclear cells in CCUS. These hypermethylated sites are associated with leukocyte function and immune response and ETS-related and C/EBP-related transcription factor motifs. While the majority of TET2- associated hypermethylation sites are shared between CHIP and in AML, we find a set of AML-specific hypermethylated loci at active enhancer elements in hematopoietic stem cells. In summary, we show that TET2 mutations is associated with hypermethylated enhancers involved in myeloid differentiation in both CHIP, CCUS and AML patients. TET2 mutations are frequent in myeloid malignancies and in elderly individuals with or without cytopenia. Here, the authors analyse the association between TET2 mutations and methylation changes in healthy elderly twins and patients with cytopenia and compare them to those from leukemia.

This paper presents the plant information included in the eBASIS (BioActive Substances in Foods Information System) database on composition and biological activity of selected bioactive compounds from European plant/mushroom foods with putative beneficial and/or toxic effects. The European Food Information Resource (EuroFIR)-NETTOX Plant List (2007) presents scientific and vernacular names in 15 European languages for around 325 major European plant/mushroom foods and also for different parts of these foods. This list and its predecessor, the NETTOX List of Food Plants, have been used by national food authorities and within the European Union for consideration of plants and mushrooms that have been used to a significant degree up to 1997 and are therefore not covered by the novel food regulation (European Parliament and Council of the European Union, 1997). The species and the plant part studied are insufficiently characterised in many scientific papers. This paper informs about the naming of plants and mushrooms as an aid for scientists who are not botanists or mycologists themselves. Knowledge on scientific names used, including synonyms, may also be important for finding all relevant papers when searching the literature. In many cases, vernacular/trivial names in, for example, English do not uniquely identify the species. Finally, recommendations are given to assist researchers and reviewers of papers dealing with botanical/mycological information.

Orally administered recombinant Salmonella vaccines represent an attractive option for mass vaccination programmes against various infectious diseases. Therefore, it is crucial to gather knowledge about the possible impact of preexisiting immunity to carrier antigens on the immunogenicity of recombinant vaccines. Thirteen volunteers were preimmunized with Salmonella typhi Ty21a in order to evaluate the effects of prior immunization with the carrier strain. Then, they received three doses of 1–2×10 10 viable organisms of either the vaccine strain S. typhi Ty21a (pDB1) expressing subunits A and B of recombinant Helicobacter pylori urease ( n=9), or placebo strain S. typhi Ty21a ( n=4). Four volunteers were preimmunized and boosted with the vaccine strain S. typhi Ty21a (pDB1). No serious adverse effects were observed in any of the volunteers. Whereas none of the volunteers primed and boosted with the vaccine strain responded to the recombinant antigen, five of the nine volunteers preimmunized with the carrier strain showed cellular immune responses to H. pylori urease (56%). This supports the results of a previous study in non-preimmunized volunteers where 56% (five of nine) of the volunteers showed a cellular immune response to urease after immunisation with S. typhi Ty21a (pDB1).

Background: Arsenic is a well-known carcinogen, which is often found in drinking-water. Epidemiologic studies have shown increased cancer risks among individuals exposed to high concentrations of arsenic in drinking-water, whereas studies of the carcinogenic effect of low doses have had inconsistent results. Objective: Our aim was to determine if exposure to low levels of arsenic in drinking-water in Denmark is associated with an increased risk for cancer. Methods: The study was based on a prospective Danish cohort of 57,053 persons in the Copenhagen and Aarhus areas. Cancer cases were identified in the Danish Cancer Registry, and the Danish civil registration system was used to trace and geocode residential addresses of the cohort members. We used a geographic information system to link addresses with water supply areas, then estimated individual exposure to arsenic using residential addresses back to 1970. Average exposure for the cohort ranged between 0.05 and 25.3 microg/L (mean = 1.2 microg/L). Cox's regression models were used to analyze possible relationships between arsenic and cancer. Results: We found no significant association between exposure to arsenic and risk for cancers of the lung, bladder, liver, kidney, prostate, or colorectum, or melanoma skin cancer; however, the risk for non-melanoma skin cancer decreased with increasing exposure (incidence rate ratio = 0.88/microg/L average exposure; 95% confidence interval, 0.84-0.94). Results adjusted for enrollment area showed no association with non-melanoma skin cancer. Conclusions: The results indicate that exposure to low doses of arsenic might be associated with a reduced risk for skin cancer.

A new homalorhagid genus and species, Mixtophyes abyssalis gen. et sp. nov., is described from the deep-sea of the Guinea Basin in the Atlantic Ocean. The new genus and species was collected during the R/V Meteor Diva2 M63/2 Cruise, and it is characterized by a trunk with segment 1 consisting of a tergal and a single sternal plate, without any subdivisions or differentiations, segment 2–10 of one tergal and two sternal plates and segment 11 of a tergal and a sternal plate. Lateral terminal spines are present in both sexes. As part of the study of the new taxon, the type material of Neocentrophyes intermedius and N. satyai was re-examined, and new information is provided for both species. Based on the information from Mixtophyes abyssalis gen. et sp. nov. and re-examination of the two Neocentrophyes species, emended diagnoses for Neocentrophyes and Neocentrophyidae are proposed, and an updated identification key to homalorhagid genera and species of Neocentrophyidae is provided. Mixtophyes abyssalis gen. et sp. nov. is tentatively assigned to Neocentrophyidae, but evaluation of our current hypotheses about homalorhagid evolution and phylogeny also indicated that the family most probably is paraphyletic and that revision of homalorhagid classification is required when new results from phylogenetic analyses become available.

Several studies have linked DNA methylation at individual CpG sites to aging and various diseases. Recent studies have also identified single CpGs whose methylation levels are associated with all-cause mortality. In this study, we perform an epigenome-wide study of the association between CpG methylation and mortality in a population of 435 monozygotic twin pairs from three Danish twin studies. The participants were aged 55–90 at the time of blood sampling and were followed for up to 20 years. We validated our results by comparison with results from a British and a Swedish cohort, as well as results from the literature. We identified 2806 CpG sites associated with mortality (false discovery rate ( FDR ) < 0.05 ), of which 24 had an association p-value below 10 − 7 . This was confirmed by intra-pair comparison controlling for confounding effects. Eight of the 24 top sites could be validated in independent datasets or confirmed by previous studies. For all these eight sites, hypomethylation was associated with poor survival prognosis, and seven showed monozygotic correlations above 35%, indicating a potential moderate to strong heritability, but leaving room for substantial shared or unique environmental effects. We also set up a predictor for mortality using least absolute shrinkage and selection operator (LASSO) regression. The predictor showed good performance on the Danish data under cross-validation, but did not perform very well in independent samples.

Exposure to ultrafine particles (UFPs) from vehicle exhaust has been related to risk of cardiovascular and pulmonary disease and cancer, even though exposure assessment is difficult. We studied personal exposure in terms of number concentrations of UFPs in the breathing zone, using portable instruments in six 18-hr periods in 15 healthy nonsmoking subjects. Exposure contrasts of outdoor pollution were achieved by bicycling in traffic for 5 days and in the laboratory for 1 day. Oxidative DNA damage was assessed as strand breaks and oxidized purines in mononuclear cells isolated from venous blood the morning after exposure measurement. Cumulated outdoor and cumulated indoor exposures to UFPs each were independent significant predictors of the level of purine oxidation in DNA but not of strand breaks. Ambient air concentrations of particulate matter with an aerodynamic diameter of ≤ 10 μm ( PM10), nitrous oxide, nitrogen dioxide, carbon monoxide, and/or number concentration of UFPs at urban background or busy street monitoring stations was not a significant predictor of DNA damage, although personal UFP exposure was correlated with urban background concentrations of CO and NO2, particularly during bicycling in traffic. The results indicate that biologic effects of UFPs occur at modest exposure, such as that occurring in traffic, which supports the relationship of UFPs and the adverse health effects of air pollution.

Background: TB-403 (RO 5323441), a humanised monoclonal antibody, is a novel antiangiogenesis agent directed against placental growth factor. The safety, pharmacokinetics (PK), and antitumour activity of TB-403 were assessed in a phase I, dose-escalation study in patients with advanced solid tumours. Methods: Patients in sequential dose groups received either weekly doses of 1.25, 5.0, or 10 mg kg −1 or doses of 20 or 30 mg kg −1 every third week. Results: Twenty-three patients were enrolled and received TB-403. The most common adverse events (AEs) were fatigue, constipation, pyrexia, dyspnoea, and nausea. One serious AE, a lung embolus in a patient with non-small cell lung cancer treated with 10 mg kg −1 weekly, was deemed possibly related to TB-403. No dose-limiting toxicities were observed, and a maximum-tolerated dose was not reached. The PK parameters were dose linear and the terminal half-life values ranged from 9 to 14 days. Six patients exhibited stable disease for at least 8 weeks. Two patients, (oesophageal squamous cell carcinoma and pancreatic adenocarcinoma) both treated with 5 mg kg −1 weekly, remained stable for 12 months. Conclusion: TB-403 treatment in this patient population is well tolerated, with a safety profile distinct from that of vascular endothelial growth factor-axis inhibitors.

Collective oscillations of superfluid mixtures of ultra cold fermionic and bosonic atoms are investigated while varying the fermion-boson scattering length. We study the dynamics with respect to excited center of mass modes and breathing modes in the mixture. Parametric resonances are also analyzed when the scattering length varies periodically in time, by comparing partial differential equation (PDE) models and ordinary differential equation (ODE) models for the dynamics. An application to the recent experiment with fermionic \\(^{6}\\)Li and bosonic \\(^{7}\\)Li atoms, which approximately have the same masses, is discussed.