Robust spatially resolved pressure measurements using MRI with novel buoyant advection-free preparations of stable microbubbles in polysaccharide gels

MRI of fluids containing lipid coated microbubbles has been shown to be an effective tool for measuring the local fluid pressure. However, the intrinsically buoyant nature of these microbubbles precludes lengthy measurements due to their vertical migration under gravity and pressure-induced coalescence. A novel preparation is presented which is shown to minimize both these effects for at least 25 min. By using a 2% polysaccharide gel base with a small concentration of glycerol and 1,2-distearoyl-sn-glycero-3-phosphocholine coated gas microbubbles, MR measurements are made for pressures between 0.95 and 1.44 bar. The signal drifts due to migration and amalgamation are shown to be minimized for such an experiment whilst yielding very high NMR sensitivities up to 38% signal change per bar

Close Vicinity of PrP Expressing Cells (FDC) with Noradrenergic Fibers in Healthy Sheep Spleen

In naturally and experimentally occurring scrapie in sheep, prions invade the immune system and replicate in lymphoid organs. Here we analysed immunohistochemically, in seven spleens of 6-month-old healthy sheep, the nature of the cells expressing prion protein (PrP) potentially supporting prion replication, as well as their relationship with autonomic innervation. PrP was identified using either RB1 rabbit antiserum or 4F2 monoclonal antibody directed against AA 108–123 portion of the bovine and AA 79–92 of human prion protein respectively. Using double labelling analysis, we demonstrated that PrPc is expressed by follicular dendritic cells using a specific monoclonal antibody (CNA42). We also showed the close vicinity of these PrP expressing cells with noradrenergic fibers, using a polyclonal tyrosine hydroxylase antibody. Our results may help the study of the cellular requirements for the possible neuroinvasion from the spleen

Design and testing of microbubble‐based MRI contrast agents for gastric pressure measurement

Purpose: This work demonstrates specifically tailored microbubble‐based preparations and their suitability as MRI contrast agents for ingestion and measuring temporal and spatial pressure variation in the human stomach. Methods: Enhanced alginate spheres were prepared by incorporating gas‐filled microbubbles into sodium alginate solution followed by the polymerization of the mixture in an aqueous calcium lactate solution. The microbubbles were prepared with a phospholipid shell and perfluorocarbon gas filling, using a mechanical cavitational agitation regime. The NMR signal changes to externally applied pressure and coming from the enhanced alginate spheres were acquired and compared with that of alginate spheres without microbubbles. In vivo investigations were also carried out on healthy volunteers to measure the pressure variation in the stomach. Results: The MR signal changes in the contrast agent exhibits a linear sensitivity of approximately 40% per bar, as opposed to no measurable signal change seen in the control gas‐free spheres. This novel contrast agent also demonstrates an excellent stability in simulated gastric conditions, including at body temperature. In vivo studies showed that the signal change exhibited in the meal within the antrum region is between 5% and 10%, but appears to come from both pressure changes and partial volume artifacts. Conclusion: This study demonstrates that alginate spheres with microbubbles can be used as an MRI contrast agent to measure pressure changes. The peristaltic movement within the stomach is seen to substantially alter the overall signal intensity of the contrast agent meal. Future work must focus on improving the contrast agent's sensitivity to pressure changes

Varroa destructor mites regularly generate ultra-short, high magnitude vibrational pulses

The ectoparasitic mite Varroa destructor is considered one of the greatest threats to the honeybee Apis mellifera. To successfully manage mite populations residing in the colony, beekeepers must stay informed of infestation levels in their apiaries. The remote, non-destructive detection of Varroa mites in honeybee hives would therefore be highly desirable. Here we show that an ultra-sensitive (1000 mV/g) accelerometer can detect vibrational waveforms originating from one individual mite. We further focus on a commonly observed pulsing behaviour never before described, characterising its physical features, periodicity and strength. The spectral features of the detected pulses strongly depend on the substrate on which they are produced. The characteristics of the vibrational pulse, particularly its repeatability and strength, indicate that mite vibrations could be successfully detected in a fully populated honeybee hive. These features, combined with the remarkably high varroa muscular power output (up to 810nW) indicate that this pulse may be functional for the mite. Our results uncover an exciting novel behaviour and provide a foundation for the remote detection of mites in beehives using vibration capture

Emergence of Classical BSE Strain Properties during Serial Passages of H-BSE in Wild-Type Mice

BACKGROUND: Two distinct forms of atypical spongiform encephalopathies (H-BSE and L-BSE) have recently been identified in cattle. Transmission studies in several wild-type or transgenic mouse models showed that these forms were associated with two distinct major strains of infectious agents, which also differed from the unique strain that had been isolated from cases of classical BSE during the food-borne epizootic disease. METHODOLOGY/PRINCIPAL FINDINGS: H-BSE was monitored during three serial passages in C57BL/6 mice. On second passage, most of the inoculated mice showed molecular features of the abnormal prion protein (PrP(d)) and brain lesions similar to those observed at first passage, but clearly distinct from those of classical BSE in this mouse model. These features were similarly maintained during a third passage. However, on second passage, some of the mice exhibited distinctly different molecular and lesion characteristics, reminiscent of classical BSE in C57Bl/6 mice. These similarities were confirmed on third passage from such mice, for which the same survival time was also observed as with classical BSE adapted to C57Bl/6 mice. Lymphotropism was rarely detected in mice with H-BSE features. In contrast, PrP(d) was detectable, on third passage, in the spleens of most mice exhibiting classical BSE features, the pattern being indistinguishable from that found in C57Bl/6 mice infected with classical BSE. CONCLUSION/SIGNIFICANCE: Our data demonstrate the emergence of a prion strain with features similar to classical BSE during serial passages of H-BSE in wild-type mice. Such findings might help to explain the origin of the classical BSE epizootic disease, which could have originated from a putatively sporadic form of BSE

Assessment of subacute genotoxic and histopathological effects of a food flavour ingredient, 4-ethylbenzaldehyde (EBA) on zebrafish (Danio rerio) model

Modern food industry widely uses a variety of flavour and fragrance materials. One of the most used compound groups is the aldehydes. The benzaldehyde, also known as artificial almond oil, is one of the most commonly used flavouring in food industry nowadays. The effects of this compound on different species are well known, a lot of toxicological information can be found in the literature. 4-ethylbenzaldehyde is also a member of aldehyde group, the physical properties are similar to benzaldehyde and also has almond scent. Unlike benzaldehyde, it has no chemical safety assessment according to its chemical safety sheet, and only one experiment can be found on its effects on vertebrates. This compound can also be found at the group of flavours and fragrances. The aim of this study was to examine the subacute DNA and tissue damaging effects of EBA. The genotoxic effects of EBA in zebrafish were evaluated by using micronucleus assay. Significant increase in the micronucleus frequency had been described for all tested concentrations. Alterations were found in the liver of the fish group treated with 11 mg l–1 EBA for 21 days

A C-Terminal Protease-Resistant Prion Fragment Distinguishes Ovine “CH1641-Like” Scrapie from Bovine Classical and L-Type BSE in Ovine Transgenic Mice

The protease-resistant prion protein (PrPres) of a few natural scrapie isolates identified in sheep, reminiscent of the experimental isolate CH1641 derived from a British natural scrapie case, showed partial molecular similarities to ovine bovine spongiform encephalopathy (BSE). Recent discovery of an atypical form of BSE in cattle, L-type BSE or BASE, suggests that also this form of BSE might have been transmitted to sheep. We studied by Western blot the molecular features of PrPres in four “CH1641-like” natural scrapie isolates after transmission in an ovine transgenic model (TgOvPrP4), to see if “CH1641-like” isolates might be linked to L-type BSE. We found less diglycosylated PrPres than in classical BSE, but similar glycoform proportions and apparent molecular masses of the usual PrPres form (PrPres #1) to L-type BSE. However, the “CH1641-like” isolates differed from both L-type and classical BSE by an abundant, C-terminally cleaved PrPres product (PrPres #2) specifically recognised by a C-terminal antibody (SAF84). Differential immunoprecipitation of PrPres #1 and PrPres #2 resulted in enrichment in PrPres #2, and demonstrated the presence of mono- and diglycosylated PrPres products. PrPres #2 could not be obtained from several experimental scrapie sources (SSBP1, 79A, Chandler, C506M3) in TgOvPrP4 mice, but was identified in the 87V scrapie strain and, in lower and variable proportions, in 5 of 5 natural scrapie isolates with different molecular features to CH1641. PrPres #2 identification provides an additional method for the molecular discrimination of prion strains, and demonstrates differences between “CH1641-like” ovine scrapie and bovine L-type BSE transmitted in an ovine transgenic mouse model

A Year in the Life of the EU-CardioRNA COST Action: CA17129 Catalysing Transcriptomics Research in Cardiovascular Disease

The EU-CardioRNA Cooperation in Science and Technology (COST) Action is a European-wide consortium established in 2018 with 31 European country members and four associate member countries to build bridges between translational researchers from academia and industry who conduct research on non-coding RNAs, cardiovascular diseases and similar research areas. EU-CardioRNA comprises four core working groups (WG1-4). In the first year since its launch, EU-CardioRNA met biannually to exchange and discuss recent findings in related fields of scientific research, with scientific sessions broadly divided up according to WG. These meetings are also an opportunity to establish interdisciplinary discussion groups, brainstorm ideas and make plans to apply for joint research grants and conduct other scientific activities, including knowledge transfer. Following its launch in Brussels in 2018, three WG meetings have taken place. The first of these in Lisbon, Portugal, the second in Istanbul, Turkey, and the most recent in Maastricht, The Netherlands. Each meeting includes a scientific session from each WG. This meeting report briefly describes the highlights and key take-home messages from each WG session in this first successful year of the EU-CardioRNA COST Action. © 2020 by the authors

Structural revelations of photosynthesis' membrane protein complexes

Photosynthetic organisms appeared early in evolution and their photosynthetic apparatus has evolved along. The first bacteria carried out only anoxygenic photosynthesis catalyzed by one type of reaction center, type I or II, which somehow came together in cyanobacteria, and evolved into photosystems I and II. This was an evolutionary step that enabled cyanobacteria to carry out oxygenic photosynthesis. The photosystems have the unique capacity to perform and fix energy in a process where water splitting and oxygen evolution takes place, providing planet Earth with an essential molecule for development of life, i.e. Oxygen. Throughout evolution, primordial organisms became more complex upon colonizing diverse environments resulting into the current day sophisticated systems. Nevertheless, the photosystems have preserved their vital mechanisms of sunlight conversion with PSI at almost 100% efficiency, and PSII’s unique water splitting property. Important about photosynthesis systems are the high-energy conversion efficiency and oxygen evolution besides hydrogen generation by some organisms like cyanobacteria. These features are precious global demands for efficient sun utilizing devices, environmental concerns and current economics of alternative energy source to fossil fuel depletion. The diversity of the photosynthesis proteins due to evolution upon adaptation and exploitability is intriguing for researchers from all fields of science to understand aspects of structural diversity, function and dynamics. This work is highly complementary and has been carried out in multidisciplinary collaborations to get more impact for understanding the photosynthesis systems that evolved early or later. The results of which can be integrated into applied technology.