Endocrine disruptors (EDs) are chemicals that contribute to health problems by interfering with the physiological production and target effects of hormones, with proven impacts on a number of ...endocrine systems including the thyroid gland. Exposure to EDs has also been associated with impairment of the reproductive system and incidence in occurrence of obesity, type 2 diabetes, and cardiovascular diseases during ageing. SCREENED aims at developing in vitro assays based on rodent and human thyroid cells organized in three different three-dimensional (3D) constructs. Due to different levels of anatomical complexity, each of these constructs has the potential to increasingly mimic the structure and function of the native thyroid gland, ultimately achieving relevant features of its 3D organization including: 1) a 3D organoid based on stem cell-derived thyrocytes, 2) a 3D organoid based on a decellularized thyroid lobe stromal matrix repopulated with stem cell-derived thyrocytes, and 3) a bioprinted organoid based on stem cell-derived thyrocytes able to mimic the spatial and geometrical features of a native thyroid gland. These 3D constructs will be hosted in a modular microbioreactor equipped with innovative sensing technology and enabling precise control of cell culture conditions. New superparamagnetic biocompatible and biomimetic particles will be used to produce "magnetic cells" to support precise spatiotemporal homing of the cells in the 3D decellularized and bioprinted constructs. Finally, these 3D constructs will be used to screen the effect of EDs on the thyroid function in a unique biological sex-specific manner. Their performance will be assessed individually, in comparison with each other, and against in vivo studies. The resulting 3D assays are expected to yield responses to low doses of different EDs, with sensitivity and specificity higher than that of classical 2D in vitro assays and animal models. Supporting the "Adverse Outcome Pathway" concept, proteogenomic analysis and biological computational modelling of the underlying mode of action of the tested EDs will be pursued to gain a mechanistic understanding of the chain of events from exposure to adverse toxic effects on thyroid function. For future uptake, SCREENED will engage discussion with relevant stakeholder groups, including regulatory bodies and industry, to ensure that the assays will fit with purposes of ED safety assessment. In this project review, we will briefly discuss the current state of the art in cellular assays of EDs and how our project aims at further advancing the field of cellular assays for EDs interfering with the thyroid gland.
Neutrophils are classically characterized as merely reactive innate effector cells. However, the microbiome is known to shape the education and maturation process of neutrophils, improving their ...function and immune-plasticity. Recent reports demonstrate that murine neutrophils possess the ability to exert adaptive responses after exposure to bacterial components such as LPS (Gram-negative bacteria) or LTA (Gram-positive bacteria). We now ask whether small extracellular vesicles (EVs) from the gut may directly mediate adaptive responses in neutrophils in vitro. Murine bone marrow-derived neutrophils were primed in vitro by small EVs of high purity collected from colon stool samples, followed by a second hit with LPS. We found that low-dose priming with gut microbiota-derived small EVs enhanced pro-inflammatory sensitivity as indicated by elevated levels of TNF-α, IL-6, ROS and MCP-1 and increased migratory and phagocytic activity. In contrast, high-dose priming resulted in a tolerant phenotype, marked by increased IL-10 and decreased transmigration and phagocytosis. Alterations in TLR2/MyD88 as well as TLR4/MyD88 signaling were correlated with the induction of adaptive cues in neutrophils in vitro. Taken together, our study shows that small EVs from stools can drive adaptive responses in neutrophils in vitro and may represent a missing link in the gut-immune axis.
Fiber-optic microsensors with a tip diameter of ∼140 μm have been developed that enable simultaneous measurement of dissolved oxygen (DO) and pH, and of DO and temperature (T), respectively. The tip ...of the optical fiber was covered with sensor compositions based on luminescent microbeads that respond to the respective parameters by a change in the decay time, intensity of their luminescence, or both. The use of microbeads enables the ratio of the signals to be easily varied, reduces the risk of fluorescence energy transfer between indicator dyes, and reduces the adverse effect of singlet oxygen that is produced in the oxygen-sensitive beads. The sensor chemistry for DO/pH was modified
In this study, various wood material sources were used for the manufacture of wood-polymer composites (WPC). The materials were categorised as virgin wood particles (VWP), reprocessed WPC particles ...(RWP) and recycled thermoset composite particles (RCP) and derived from two virgin wood sources, three-layer particleboards, medium-density fibreboards (MDF) boards, or two different wood/polypropylene composites. All produced wood-polypropylene compounds contained 60% wood material and were manufactured using a co-rotating extruder. Malleated polypropylene was used as a coupling agent. Specimens were injection moulded and subsequently tested for their physico-mechanical properties. To characterize particles before and after processing, dynamic image analysis (DIA) measurement were performed. Additionally, X-ray micro-computed tomography (XµCT) was used to characterize the internal structure of the composites and to verify the obtained particle’s characteristics. It was found that length and aspect ratio of particles were remarkably different before and after processing (loss in length of 15–70% and aspect ratio of 10–40%). Moreover, there were notably differences between the particle sources (RCP retained the highest length and aspect ratio values, followed by VWP and RWP). The results suggest that increased aspect ratios can indeed significantly improve mechanical properties (up to 300% increase in impact bending strength and 75% increase in tensile strength, comparing WPC based either on virgin spruce or MDF material). This phenomenon is suggested to be partially superimposed by improved dispersion of particles, which is expected due to lower variance and increased mechanical properties of RWP composites. However, no notable alterations were observed for composite density. Reprocessed WPC and, particularly, RCP material have proved to be an appealing raw material substitute for the manufacturing of wood–polymer composites.
MASCOT, the Mobile Asteroid Surface SCOuT, is a small lander jointly developed by the German and French space agencies Ho et al., 2017, that travelled on board of the JAXA Hayabusa2 spacecraft for ...over 3 years to the C-type asteroid Ryugu. The goal of MASCOT was to perform in situ measurements on the surface of the asteroid by means of its four scientific instruments, substantially contributing in this way to the overall scientific return of Hayabusa2 mission.
The objective of the paper is to provide a detailed overview of the Landing Site Selection Process (LSSP) for MASCOT, from the preliminary design phase that started several years before launch, up to the actual execution of the selection process and its operational implementation. The effort that was put on the LSSP by all the teams involved over all these years was one of the key elements, leading to the unprecedented success of this mission.
The ultrastable low-noise current amplifier (ULCA) was developed as an advanced instrument for the improved measurement of currents generated by single-electron transport (SET) devices. It was ...optimized for direct currents in the picoampere range, and achieves an uncertainty of <;0.1 μA/A for a current of 100 pA typically generated by SET pumps. This paper summarizes our efforts in extending the ULCA's current range and minimizing the measurement uncertainty over a wide range. Two ULCA variants with improved shortterm uncertainty of about 0.02 μA/A or improved noise level of 1.4 fA/√Hz are presented. Combining these devices allows the construction of a novel standard for direct currents below 50 μA, which has superior performance to previous methods for small-current generation or measurement. ULCAs involving √ thick-film resistors achieve noise levels down to 0.43 fA/√Hz. A low-bias variant features an effective input bias current within ±100 aA and a temperature coefficient within ±10 aA/K, which enables uncertainties below 10 aA in direct current measurements without reversing or switching ON/OFF the signal current.
A novel ionization gauge was developed where the electron beam is guided through the ionization space in a straight path. This design was chosen in order to develop a more stable ionization vacuum ...gauge suitable as reference standard in the range of 10−6 Pa to 10−2 Pa. The design requires a low electron current resulting in even lower ion currents. For the purpose of a reference standard, these ultra-low currents in the range 1 pA–100 nA need to be measured in a traceable manner. For the first time, an ultrastable low-noise current amplifier was used for this purpose.
A new family of coumarin-based pH indicators was synthesized. They are sensitive to pH in either weakly acidic or weakly basic solution. The indicators possess moderate to high brightness, excellent ...photostability and compatibility with light-emitting diodes. The indicators were covalently immobilized on the surface of amino-modified polymer microbeads which in turn were incorporated into a hydrogel matrix to obtain novel pH-sensitive materials. When a mixture of two different microbeads is used, the membranes are capable of optical pH sensing over a very wide range comparable to the dynamic range of the glass electrode (pH 1-11).
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