Systems Biology in ELIXIR: modelling in the spotlight

info:eu-repo/semantics/publishedVersio

Translations equations to compare ActiGraph GT3X and Actical accelerometers activity counts

Background: This study aimed to develop a translation equation to enable comparison between Actical and ActiGraph GT3X accelerometer counts recorded minute by minute. Methods: Five males and five females of variable height, weight, body mass index and age participated in this investigation. Participants simultaneously wore an Actical and an ActiGraph accelerometer for two days. Conversion algorithms and R2 were calculated day by day for each subject between the omnidirectional Actical and three different ActiGraph (three-dimensional) outputs: 1) vertical direction, 2) combined vector, and 3) a custom vector. Three conversion algorithms suitable for minute/minute conversions were then calculated from the full data set. Results: The vertical ActiGraph activity counts demonstrated the closest relationship with the Actical, with consistent moderate to strong conversions using the algorithm: y = 0.905x, in the day by day data (R2 range: 0.514 to 0.989 and average: 0.822) and full data set (R2 = 0.865). Conclusions: The Actical is most sensitive to accelerations in the vertical direction, and does not closely correlate with three-dimensional ActiGraph output. Minute by minute conversions between the Actical and ActiGraphvertical component can be confidently performed between data sets and might allow further synthesis of information between studies

Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes

BACKGROUND:DNA methylation is affected by the activities of the key enzymes and intermediate metabolites of the one-carbon pathway, one of which involves homocysteine. We investigated the effect of the well-known genetic variant associated with mildly elevated homocysteine: MTHFR 677C>T independently and in combination with other homocysteine-associated variants, on genome-wide leukocyte DNA-methylation. METHODS:Methylation levels were assessed using Illumina 450k arrays on 9,894 individuals of European ancestry from 12 cohort studies. Linear-mixed-models were used to study the association of additive MTHFR 677C>T and genetic-risk score (GRS) based on 18 homocysteine-associated SNPs, with genome-wide methylation. RESULTS:Meta-analysis revealed that the MTHFR 677C>T variant was associated with 35 CpG sites in cis, and the GRS showed association with 113 CpG sites near the homocysteine-associated variants. Genome-wide analysis revealed that the MTHFR 677C>T variant was associated with 1 trans-CpG (nearest gene ZNF184), while the GRS model showed association with 5 significant trans-CpGs annotated to nearest genes PTF1A, MRPL55, CTDSP2, CRYM and FKBP5. CONCLUSIONS:Our results do not show widespread changes in DNA-methylation across the genome, and therefore do not support the hypothesis that mildly elevated homocysteine is associated with widespread methylation changes in leukocytes

Lung epithelium as a sentinel and effector system in pneumonia – molecular mechanisms of pathogen recognition and signal transduction

Pneumonia, a common disease caused by a great diversity of infectious agents is responsible for enormous morbidity and mortality worldwide. The bronchial and lung epithelium comprises a large surface between host and environment and is attacked as a primary target during lung infection. Besides acting as a mechanical barrier, recent evidence suggests that the lung epithelium functions as an important sentinel system against pathogens. Equipped with transmembranous and cytosolic pathogen-sensing pattern recognition receptors the epithelium detects invading pathogens. A complex signalling results in epithelial cell activation, which essentially participates in initiation and orchestration of the subsequent innate and adaptive immune response. In this review we summarize recent progress in research focussing on molecular mechanisms of pathogen detection, host cell signal transduction, and subsequent activation of lung epithelial cells by pathogens and their virulence factors and point to open questions. The analysis of lung epithelial function in the host response in pneumonia may pave the way to the development of innovative highly needed therapeutics in pneumonia in addition to antibiotics

LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our “modern” postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases

Precision Measurement of Cosmic-Ray Nitrogen and its Primary and Secondary Components with the Alpha Magnetic Spectrometer on the International Space Station

A precision measurement of the nitrogen flux with rigidity (momentum per unit charge) from 2.2 GV to 3.3 TV based on 2.2 x 10(6) events is presented. The detailed rigidity dependence of the nitrogen flux spectral index is presented for the first time. The spectral index rapidly hardens at high rigidities and becomes identical to the spectral indices of primary He, C, and O cosmic rays above similar to 700 GV. We observed that the nitrogen flux Phi(N) can be presented as the sum of its primary component Phi(P)(N) and secondary component Phi(S)(N), Phi(N) = Phi(P)(N) + Phi(S)(N), and we found Phi(N) is well described by the weighted sum of the oxygen flux Phi(O) (primary cosmic rays) and the boron flux Phi(B) (secondary cosmic rays), with Phi(P)(N) = (0.090 +/- 0.002) x Phi(O) and Phi(S)(N) = (0.62 +/- 0.02) x Phi(B) over the entire rigidity range. This corresponds to a change of the contribution of the secondary cosmic ray component in the nitrogen flux from 70% at a few GV to < 30% above 1 TV

Observation of New Properties of Secondary Cosmic Rays Lithium, Beryllium, and Boron by the Alpha Magnetic Spectrometer on the International Space Station

We report on the observation of new properties of secondary cosmic rays Li, Be, and B measured in the rigidity (momentum per unit charge) range 1.9 GV to 3.3 TV with a total of 5.4 x 10(6) nuclei collected by AMS during the first five years of operation aboard the International Space Station. The Li and B fluxes have an identical rigidity dependence above 7 GV and all three fluxes have an identical rigidity dependence above 30 GV with the Li/Be flux ratio of 2.0 +/- 0.1. The three fluxes deviate from a single power law above 200 GV in an identical way. This behavior of secondary cosmic rays has also been observed in the AMS measurement of primary cosmic rays He, C, and O but the rigidity dependences of primary cosmic rays and of secondary cosmic rays are distinctly different. In particular, above 200 GV, the secondary cosmic rays harden more than the primary cosmic rays