Association of the biomarkers soluble ST2, galectin-3 and growth-differentiation factor-15 with heart failure and other non-cardiac diseases

AbstractBackgroundThe biomarkers soluble ST2 (sST2), galectin-3, and growth-differentiation factor-15 (GDF-15) provide prognostic information in patients with heart failure (HF). The aim of this study was to evaluate to which extent plasma concentrations of these biomarkers are increased in HF compared with diverse non-cardiac conditions such as infectious disease or chronic kidney disease.MethodsWe recruited 15 patients in each of the following clinical categories: HF without co-morbidity, pneumonia without co-morbidity, chronic obstructive pulmonary disease (COPD) without co-morbidity, HF and a co-morbidity of pneumonia, renal disease without co-morbidity, and sepsis. We used 22 healthy individuals as control group. In each of the 112 study participants, we measured plasma concentrations of sST2 (Presage assay), galectin-3 (Abbott assay) and GDF-15 (Roche assay).ResultsCompared to controls, the median sST2 concentration was ~2.5-fold increased in HF, ~3.5-fold in pneumonia, ~5.0-fold in COPD, ~5.8-fold in HF+pneumonia, and ~70-fold in sepsis (p<0.001 for all). sST2 was not significantly increased in renal disease. Compared to controls, the median galectin-3 concentration was ~1.5-fold increased in HF, ~1.4-fold in pneumonia, ~2.4-fold in HF+pneumonia, ~2.5-fold in renal disease, and ~2.7-fold in sepsis (p<0.001 for all). Galectin-3 was not significantly increased in COPD. Compared to controls, the median GDF-15 concentration was ~4.4-fold increased in HF, ~5.4-fold in pneumonia, ~2.1-fold in COPD, ~8.3-fold in HF+pneumonia, ~5.1-fold in renal disease, and ~27-fold in sepsis (p<0.001). In the 112 study participants, correlation analyses revealed a relatively strong association between galectin-3 and GDF-15 (correlation coefficient, 0.739; p<0.001).ConclusionBecause increased plasma concentrations of sST2, galectin-3, and GDF-15 are not specific for a distinct disease group, the three biomarkers are not useful for diagnostic purposes. The results of our study are novel with respect to sST2, galectin-3 and GDF-15 as markers of inflammatory diseases and should encourage further studies

Evaluation of novel inducible promoter/repressor systems for recombinant protein expression in Lactobacillus plantarum

Background: Engineering lactic acid bacteria (LAB) is of growing importance for food and feed industry as well as for in vivo vaccination or the production of recombinant proteins in food grade organisms. Often, expression of a transgene is only desired at a certain time point or period, e.g. to minimize the metabolic burden for the host cell or to control the expression time span. For this purpose, inducible expression systems are preferred, though cost and availability of the inducing agent must be feasible. We selected the plasmid free strain Lactobacillus plantarum 3NSH for testing and characterization of novel inducible promoters/repressor systems. Their feasibility in recombinant protein production was evaluated. Expression of the reporter protein mCherry was monitored with the BioLector® micro-fermentation system. Results: Reporter gene mCherry expression was compared under the control of different promoter/repressor systems: PlacA (an endogenous promoter/repressor system derived from L. plantarum 3NSH), PxylA (a promoter/repressor system derived from Bacillus megaterium DSMZ 319) and PlacSynth (synthetic promoter and codon-optimized repressor gene based on the Escherichia coli lac operon). We observed that PlacA was inducible solely by lactose, but not by non-metabolizable allolactose analoga. PxylA was inducible by xylose, yet showed basal expression under non-induced conditions. Growth on galactose (as compared to exponential growth phase on glucose) reduced basal mCherry expression at non-induced conditions. PlacSynth was inducible with TMG (methyl -D-thiogalactopyranoside) and IPTG (isopropyl -D-1-thiogalactopyranoside), but also showed basal expression without inducer. The promoter PlacSynth was used for establishment of a dual plasmid expression system, based on T7 RNA polymerase driven expression in L. plantarum. Comparative Western blot supported BioLector® micro-fermentation measurements. Conclusively, overall expression levels were moderate (compared to a constitutive promoter). Conclusions: We evaluated different inducible promoters, as well as an orthologous expression system, for controlled gene expression in L. plantarum. Furthermore, here we provide proof of concept for a T7 RNA polymerase based expression system for L. plantarum. Thereby we expanded the molecular toolbox for an industrial relevant and generally regarded as safe (GRAS) strain.(VLID)101641

Comparison of a standard CO2 pressure pneumoperitoneum insufflator versus AirSeal™: study protocol of a randomized controlled trial

BACKGROUND: AirSeal™ is a novel class of valve-free insufflation system that enables a stable pneumoperitoneum with continuous smoke evacuation and carbon dioxide (CO(2)) recirculation during laparoscopic surgery. Comparison data to standard CO(2) pressure pneumoperitoneum insufflators is scarce. The aim of this study is to evaluate the potential advantages of AirSeal™ compared to a standard CO(2) insufflator. METHODS/DESIGN: This is a single center randomized controlled trial comparing elective laparoscopic cholecystectomy, colorectal surgery and hernia repair with AirSeal™ (group A) versus a standard CO(2) pressure insufflator (group S). Patients are randomized using a web-based central randomization and registration system. Primary outcome measures will be operative time and level of postoperative shoulder pain by using the visual analog score (VAS). Secondary outcomes include the evaluation of immunological values through blood tests, anesthesiological parameters, surgical side effects and length of hospital stay. Taking into account an expected dropout rate of 5%, the total number of patients is 182 (n = 91 per group). All tests will be two-sided with a confidence level of 95% (P <0.05). DISCUSSION: The duration of an operation is an important factor in reducing the patient’s exposure to CO(2) pneumoperitoneum and its adverse consequences. This trial will help to evaluate if the announced advantages of AirSeal™, such as clear sight of the operative site and an exceptionally stable working environment, will facilitate the course of selected procedures and influence operation time and patients clinical outcome. TRIAL REGISTRATION: ClinicalTrials.gov NCT01740011, registered 23 November 2012

The Evolution of Expressing and Exchanging Cyber-Investigation Information in a Standardized Form

The growing number of investigations involving digital traces from various data sources is driving the demand for a standard way to represent and exchange pertinent information. Enabling automated combination and correlation of cyber-investigation information from multiple systems or organizations enables more efficient and comprehensive analysis, reducing the risk of mistakes and missed opportunities. These needs are being met by the evolving open-source, community-developed specification language called CASE, the Cyber-investigation Analysis Standard Expression. CASE leverages the Unified Cyber Ontology (UCO), which abstracts and expresses concepts that are common across multiple domains. This paper introduces CASE and UCO, explaining how they improve upon prior related work. The value of fully-structured data, representing provenance, and action lifecycles are discussed. The guiding principles of CASE and UCO are presented, and illustrative examples of CASE are provided using the default JSON-LD serialization

Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation

Postreplicative maintenance of genomic methylation patterns was proposed to depend largely on the binding of DNA methyltransferase 1 (Dnmt1) to PCNA, a core component of the replication machinery. We investigated how the slow and discontinuous DNA methylation could be mechanistically linked with fast and processive DNA replication. Using photobleaching and quantitative live cell imaging we show that Dnmt1 binding to PCNA is highly dynamic. Activity measurements of a PCNA-binding-deficient mutant with an enzyme-trapping assay in living cells showed that this interaction accounts for a 2-fold increase in methylation efficiency. Expression of this mutant in mouse dnmt1−/− embryonic stem (ES) cells restored CpG island methylation. Thus association of Dnmt1 with the replication machinery enhances methylation efficiency, but is not strictly required for maintaining global methylation. The transient nature of this interaction accommodates the different kinetics of DNA replication and methylation while contributing to faithful propagation of epigenetic information

The Verdon

International audienc

The Var

International audienc