Methyl jasmonate treatment affects the regulation of the 2-C-methyl-D-erythritol 4-phosphate pathway and early steps of the triterpenoid biosynthesis in Chlamydomonas reinhardtii

© 2019 Elsevier B.V. Terpenoids are a large and diverse class of naturally occurring metabolites serving many industrial applications and natural roles. Economically important terpenoids are often produced in low abundance from their natural sources, making their industrial-scale production challenging or uneconomical, therefore engineered microorganisms are frequently used as heterologous production platforms. Photosynthetic microorganisms, such as the green alga Chlamydomonas reinhardtii, represent promising systems to produce terpenoids in a cost-effective and sustainable manner, but knowledge about the regulation of their terpenoid metabolism remains limited. Here we report on the investigation of the phytohormone methyl jasmonate (MeJA) as elicitor of algal terpenoid synthesis. We treated C. reinhardtii cells in mid-exponential growth phase with three different concentrations of MeJA (0.05, 0.5 and 1 mM). The highest concentration of MeJA affected the photosynthetic activity of the cells, arrested the growth and up-regulated key genes of the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, leading to a significant increase in intermediates of this pathway, squalene and (S)-2,3-epoxysqualene, while the abundance of cycloartenol, and two main sterols (ergosterol and 7-dehydroporiferasterol) decreased. These data suggest the redirection of the carbon flux towards the synthesis of yet uncharacterised triterpenoid secondary metabolites upon MeJA treatment. Our results offer important new insights into the regulation of the triterpenoid metabolism in C. reinhardtii and raise important questions on hormonal signalling in microalgae. Phytohormone treatment is tested for the first time in algae, where it holds great potential for identifying key transcriptional regulators of the MEP pathway as targets for future metabolic engineering studies for improve production of high-value triterpenoids

Specific Heat of Liquid Helium in Zero Gravity very near the Lambda Point

We report the details and revised analysis of an experiment to measure the specific heat of helium with subnanokelvin temperature resolution near the lambda point. The measurements were made at the vapor pressure spanning the region from 22 mK below the superfluid transition to 4 uK above. The experiment was performed in earth orbit to reduce the rounding of the transition caused by gravitationally induced pressure gradients on earth. Specific heat measurements were made deep in the asymptotic region to within 2 nK of the transition. No evidence of rounding was found to this resolution. The optimum value of the critical exponent describing the specific heat singularity was found to be a = -0.0127+ - 0.0003. This is bracketed by two recent estimates based on renormalization group techniques, but is slightly outside the range of the error of the most recent result. The ratio of the coefficients of the leading order singularity on the two sides of the transition is A+/A- =1.053+ - 0.002, which agrees well with a recent estimate. By combining the specific heat and superfluid density exponents a test of the Josephson scaling relation can be made. Excellent agreement is found based on high precision measurements of the superfluid density made elsewhere. These results represent the most precise tests of theoretical predictions for critical phenomena to date.Comment: 27 Pages, 20 Figure

Environmentally weathered polystyrene particles induce phenotypical and functional maturation of human monocyte-derived dendritic cells

Micro- and nanoplastics (MNP) are ubiquitously present in the environment due to their high persistence and bioaccumulative properties. Humans get exposed to MNP via various routes and consequently, they will encounter dendritic cells (DC) which are antigen-presenting cells involved in regulating immune responses. The consequences of DC exposure to MNP are an important, yet understudied, cause of concern. Therefore, this study aimed to assess the uptake and effect of MNP in vitro by exposing human monocyte-derived dendritic cells (MoDC) to virgin and environmentally weathered polystyrene (PS) particles of different sizes (0.2, 1, and 10 µm), at different concentrations ranging from 1 to 100 µg/ml. The effects of these particles were examined by measuring co-stimulatory surface marker (i.e. CD83 and CD86) expression. In addition, T-cell proliferation was measured via a mixed-leukocyte reaction (MLR) assay. The results showed that MoDC were capable of absorbing PS particles, and this was facilitated by pre-incubation in heat-inactivated (HI) plasma. Furthermore, depending on their size, weathered PS particles in particular caused increased expression of CD83 and CD86 on MoDC. Lastly, weathered 0.2 µm PS particles were able to functionally activate MoDC, leading to an increase in T-cell activation. These in vitro data suggest that, depending on their size, weathered PS particles might act as an immunostimulating adjuvant, possibly leading to T-cell sensitization

Overview of BioCreative II gene mention recognition.

Nineteen teams presented results for the Gene Mention Task at the BioCreative II Workshop. In this task participants designed systems to identify substrings in sentences corresponding to gene name mentions. A variety of different methods were used and the results varied with a highest achieved F1 score of 0.8721. Here we present brief descriptions of all the methods used and a statistical analysis of the results. We also demonstrate that, by combining the results from all submissions, an F score of 0.9066 is feasible, and furthermore that the best result makes use of the lowest scoring submissions

Structuring and extracting knowledge for the support of hypothesis generation in molecular biology

Background: Hypothesis generation in molecular and cellular biology is an empirical process in which knowledge derived from prior experiments is distilled into a comprehensible model. The requirement of automated support is exemplified by the difficulty of considering all relevant facts that are contained in the millions of documents available from PubMed. Semantic Web provides tools for sharing prior knowledge, while information retrieval and information extraction techniques enable its extraction from literature. Their combination makes prior knowledge available for computational analysis and inference. While some tools provide complete solutions that limit the control over the modeling and extraction processes, we seek a methodology that supports control by the experimenter over these critical processes. Results: We describe progress towards automated support for the generation of biomolecular hypotheses. Semantic Web technologies are used to structure and store knowledge, while a workflow extracts knowledge from text. We designed minimal proto-ontologies in OWL for capturing different aspects of a text mining experiment: the biological hypothesis, text and documents, text mining, and workflow provenance. The models fit a methodology that allows focus on the requirements of a single experiment while supporting reuse and posterior analysis of extracted knowledge from multiple experiments. Our workflow is composed of services from the 'Adaptive Information Disclosure Application' (AIDA) toolkit as well as a few others. The output is a semantic model with putative biological relations, with each relation linked to the corresponding evidence. Conclusion: We demonstrated a 'do-it-yourself' approach for structuring and extracting knowledge in the context of experimental research on biomolecular mechanisms. The methodology can be used to bootstrap the construction of semantically rich biological models using the results of knowledge extraction processes. Models specific to particular experiments can be constructed that, in turn, link with other semantic models, creating a web of knowledge that spans experiments. Mapping mechanisms can link to other knowledge resources such as OBO ontologies or SKOS vocabularies. AIDA Web Services can be used to design personalized knowledge extraction procedures. In our example experiment, we found three proteins (NF-Kappa B, p21, and Bax) potentially playing a role in the interplay between nutrients and epigenetic gene regulation

Samenwerking in ontwikkeling : productontwikkeling door uitbesteder en toeleverancier

Eindrapport van het project 'Kwaliteit in Innovatie door Samenwerking en Synergie". Dit rapport zat in de map, behorende bij het symposium: Partners in productontwikkeling : toeleverancier en uitbesteder; Technische Universiteit Eindhoven, 28 november 1996

The combination of carboxy-terminal propeptide of procollagen type I blood levels and late gadolinium enhancement at cardiac magnetic resonance provides additional prognostic information in idiopathic dilated cardiomyopathy - A multilevel assessment of myocardial fibrosis in dilated cardiomyopathy

Aims To determine the prognostic value of multilevel assessment of fibrosis in dilated cardiomyopathy (DCM) patients. Methods and results We quantified fibrosis in 209 DCM patients at three levels: (i) non-invasive late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR); (ii) blood biomarkers [amino-terminal propeptide of procollagen type III (PIIINP) and carboxy-terminal propeptide of procollagen type I (PICP)], (iii) invasive endomyocardial biopsy (EMB) (collagen volume fraction, CVF). Both LGE and elevated blood PICP levels, but neither PIIINP nor CVF predicted a worse outcome defined as death, heart transplantation, heart failure hospitalization, or life-threatening arrhythmias, after adjusting for known clinical predictors [adjusted hazard ratios: LGE 3.54, 95% confidence interval (CI) 1.90-6.60; P < 0.001 and PICP 1.02, 95% CI 1.01-1.03; P = 0.001]. The combination of LGE and PICP provided the highest prognostic benefit in prediction (likelihood ratio test P = 0.007) and reclassification (net reclassification index: 0.28, P = 0.02; and integrated discrimination improvement index: 0.139, P = 0.01) when added to the clinical prediction model. Moreover, patients with a combination of LGE and elevated PICP (LGE+/PICP+) had the worst prognosis (log-rank P < 0.001). RNA-sequencing and gene enrichment analysis of EMB showed an increased expression of pro-fibrotic and pro-inflammatory pathways in patients with high levels of fibrosis (LGE+/PICP+) compared to patients with low levels of fibrosis (LGE-/PICP-). This would suggest the validity of myocardial fibrosis detection by LGE and PICP, as the subsequent generated fibrotic risk profiles are associated with distinct cardiac transcriptomic profiles. Conclusion The combination of myocardial fibrosis at CMR and circulating PICP levels provides additive prognostic value accompanied by a pro-fibrotic and pro-inflammatory transcriptomic profile in DCM patients with LGE and elevated PICP