Environmental Enrichment Enhances Cav 2.1 Channel-Mediated Presynaptic Plasticity in Hypoxic–Ischemic Encephalopathy

Hypoxic–ischemic encephalopathy (HIE) is a devastating neonatal brain condition caused by lack of oxygen and limited blood flow. Environmental enrichment (EE) is a classic paradigm with a complex stimulation of physical, cognitive, and social components. EE can exert neuroplasticity and neuroprotective effects in immature brains. However, the exact mechanism of EE on the chronic condition of HIE remains unclear. HIE was induced by a permanent ligation of the right carotid artery, followed by an 8% O₂ hypoxic condition for 1 h. At 6 weeks of age, HIE mice were randomly assigned to either standard cages or EE cages. In the behavioral assessments, EE mice showed significantly improved motor performances in rotarod tests, ladder walking tests, and hanging wire tests, compared with HIE control mice. EE mice also significantly enhanced cognitive performances in Y-maze tests. Particularly, EE mice showed a significant increase in Ca_v 2.1 (P/Q type) and presynaptic proteins by molecular assessments, and a significant increase of Ca_v 2.1 in histological assessments of the cerebral cortex and hippocampus. These results indicate that EE can upregulate the expression of the Ca_v 2.1 channel and presynaptic proteins related to the synaptic vesicle cycle and neurotransmitter release, which may be responsible for motor and cognitive improvements in HIE.     

A thermal perspective of flash sintering: The effect of AC current ramp rate on microstructure evolution

In flash sintering experiments, the thermal history of the sample is key to understanding the mechanisms underlying densification rate and final properties. By combining robust temperature measurements with current-ramp-rate control, this study examined the effects of the thermal profile on the flash sintering of yttria-stabilized zirconia, with experiments ranging from a few seconds to several hours. The final density was maximized at slower heating rates, although processes slower than a certain threshold led to grain growth. The amount of grain growth observed was comparable to a similar conventional thermal process. The bulk electrical conductivity correlated with the maximum temperature and cooling rate. The only property that exhibited behavior that could not be attributed to solely the thermal profile was the grain boundary conductivity, which was consistently higher than conventional in flash sintered samples. These results suggest that, during flash sintering, athermal electric field effects are relegated to the grain boundary.     

Maternal Responses and Adaptive Changes to Environmental Stress via Chronic Nanomaterial Exposure: Differences in Inter and Transgenerational Interclonal Broods of Daphnia magna

There is increasing recognition that environmental nano-biological interactions in model species, and the resulting effects on progeny, are of paramount importance for nanomaterial (NM) risk assessment. In this work, Daphnia magna F0 mothers were exposed to a range of silver and titanium dioxide NMs. The key biological life history traits (survival, growth and reproduction) of the F1 intergenerations, at the first (F1B1), third (F1B3) and fifth (F1B5) broods, were investigated. Furthermore, the F1 germlines of each of the three broods were investigated over 3 more generations (up to 25 days each) in continuous or removed-from NM exposure, to identify how the length of maternal exposure affects the resulting clonal broods. Our results show how daphnids respond to NM-induced stress, and how the maternal effects show trade-offs between growth, reproduction and survivorship. The F1B1 (and following germline) had the shortest F0 maternal exposure times to the NMs, and thus were the most sensitive showing reduced size and reproductive output. The F1B3 generation had a sub-chronic maternal exposure, whereas the F1B5 generation suffered chronic maternal exposure where (in most cases) the most compensatory adaptive effects were displayed in response to the prolonged NM exposure, including enhanced neonate output and reduced gene expression. Transgenerational responses of multiple germlines showed a direct link with maternal exposure time to ‘sub-lethal’ effect concentrations of NMs (identified from standard OECDs acute toxicity tests which chronically presented as lethal) including increased survival and production of males in the F1B3 and G1B5 germlines. This information may help to fine-tune environmental risk assessments of NMs and prediction of their impacts on environmental ecology.     

Changes in the content and antioxidative activity of β-carotene and its metabolite vitamin A during gastrointestinal digestion and absorption and optimisation of HPLC-based detection

The β-Carotene (BC), an important precursor of vitamin A (VA), possesses antioxidant activity but is fat-soluble and has low bioavailability. In previous in-vitro assays evaluating antioxidant and 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) free radical scavenging, both BC and VA showed a strong ability to scavenge radicals and protected cells from oxidative stress. Here, we used artificially simulated gastrointestinal digestion and Caco-2 cell absorption models to evaluate the bioavailability of the BC during gastrointestinal digestion and absorption using high-performance liquid chromatography (HPLC) analysis. We observed high absorptive and transfer rates of BC and detected retinol metabolites (Vitamin A). Therefore, BC can be detected in the acidic gastrointestinal environment using HPLC. Optimised method provided better separation of BC and VA in the column, improving the accuracy of the test results.     

Aminoacyl-tRNA Synthetases as Valuable Targets for Antimicrobial Drug Discovery

Aminoacyl-tRNA synthetases (aaRSs) catalyze the esterification of tRNA with a cognate amino acid and are essential enzymes in all three kingdoms of life. Due to their important role in the translation of the genetic code, aaRSs have been recognized as suitable targets for the development of small molecule anti-infectives. In this review, following a concise discussion of aaRS catalytic and proof-reading activities, the various inhibitory mechanisms of reported natural and synthetic aaRS inhibitors are discussed. Using the expanding repository of ligand-bound X-ray crystal structures, we classified these compounds based on their binding sites, focusing on their ability to compete with the association of one, or more of the canonical aaRS substrates. In parallel, we examined the determinants of species-selectivity and discuss potential resistance mechanisms of some of the inhibitor classes. Combined, this structural perspective highlights the opportunities for further exploration of the aaRS enzyme family as antimicrobial targets.     

As the number falls,alternatives to the Hagberg–Perten falling number method: A review

This review examines the application, limitations, and potential alternatives to the Hagberg–Perten falling number (FN) method used in the global wheat industry for detecting the risk of poor end-product quality mainly due to starch degradation by the enzyme α-amylase. By viscometry, the FN test indirectly detects the presence of α-amylase, the primary enzyme that digests starch. Elevated α-amylase results in low FN and damages wheat product quality resulting in cakes that fall, and sticky bread and noodles. Low FN can occur from preharvest sprouting (PHS) and late maturity α-amylase (LMA). Moist or rainy conditions before harvest cause PHS on the mother plant. Continuously cool or fluctuating temperatures during the grain filling stage cause LMA. Due to the expression of additional hydrolytic enzymes, PHS has a stronger negative impact than LMA. Wheat grain with low FN/high α-amylase results in serious losses for farmers, traders, millers, and bakers worldwide. Although blending of low FN grain with sound wheat may be used as a means of moving affected grain through the marketplace, care must be taken to avoid grain lots from falling below contract-specified FN. A large amount of sound wheat can be ruined if mixed with a small amount of sprouted wheat. The FN method is widely employed to detect α-amylase after harvest. However, it has several limitations, including sampling variability, high cost, labor intensiveness, the destructive nature of the test, and an inability to differentiate between LMA and PHS. Faster, cheaper, and more accurate alternatives could improve breeding for resistance to PHS and LMA and could preserve the value of wheat grain by avoiding inadvertent mixing of high- and low-FN grain by enabling testing at more stages of the value stream including at harvest, delivery, transport, storage, and milling. Alternatives to the FN method explored here include the Rapid Visco Analyzer, enzyme assays, immunoassays, near-infrared spectroscopy, and hyperspectral imaging.     

Biofortification with selenium and lithium improves nutraceutical properties of major winery grapes in the Midwestern United States

Enriching the micronutrients, selenium (Se) and lithium (Li), in grapes to improve their nutraceutical properties were implemented by foliar application of organic fertiliser rich in Se and Li onto five grape cultivars. The effects of this biofortification on vine vigour, fruit quality, overall micronutrients and phenolic compounds also were investigated. Agronomic biofortification was found greatly increased the Se and Li content in the whole grape by multiple times, meanwhile it did not significantly affect the vine vigour and fruit quality of grapes. However, the biofortification did impact the Ionome (including all the mineral nutrients and trace elements) and phenolic compounds in grapes and this varied among cultivars. This study demonstrated foliar spray of organic Se/Li fertiliser was a very effective strategy to biofortify these micronutrients in grape berries, particularly in the skin, and therefore might be a promising strategy to increase the consumption and awareness of these grapes.     

Combining 1,3-Ditriazolylbenzene and Quinoline to Discover a New G-Quadruplex-Interactive Small Molecule Active against Cancer Stem-Like Cells

Quadruplex nucleic acids are promising targets for cancer therapy. In this study we used a fragment-based approach to create new flexible G-quadruplex (G4) DNA-interactive small molecules with good calculated oral drug-like properties, based on quinoline and triazole heterocycles. G4 melting temperature and polymerase chain reaction (PCR)-stop assays showed that two of these compounds are selective G4 ligands, as they were able to induce and stabilize G4s in a dose- and DNA sequence-dependent manner. Molecular docking studies have suggested plausible quadruplex binding to both the G-quartet and groove, with the quinoline module playing the major role. Compounds were screened for cytotoxicity against four cancer cell lines, where 4,4′-(4,4′-(1,3-phenylene)bis(1H-1,2,3-triazole-4,1-diyl))bis(1-methylquinolin-1-ium) ( 1 d ) showed the greater activity. Importantly, dose–response curves show that 1 d is cytotoxic in the human colon cancer HT-29 cell line enriched in cancer stem-like cells, a subpopulation of cells implicated in chemoresistance. Overall, this study identified a new small molecule as a promising lead for the development of drugs targeting G4 in cancer stem cells.     

A web-based 3D ontology navigation system for spinal disease diagnosis

The Journal of Supercomputing - This paper presents a web-based three-dimensional (3D) navigation system for a spinal disease ontology using a 3D virtual human spine. The 3D navigation system...     

Extrusion of highly filled flexible polymer sheet

Highly-filled polymer systems include color masterbatches, feedstocks for powder injection molding, and rigid sheets with high levels of flame retardants, but they have not been explored for flexible sheet. This work investigated the (a) selecting a polymer matrix with enough melt strength and flexibility to form a stable sheet with high filler loading, (b) the maximum achievable filler loading for the sheet, and (c) optimizing the process of extruding a highly-filled flexible polymer system. Extrusion grade low-density polyethylene (LDPE) provided sufficient flexibility and permitted a maximum filler loading of 36 vol% (~78 wt%). Good dispersion of the nanoparticle filler, however, required two passes through multiple screw extruders and a small reduction in the viscosity of the LDPE. Sheet with thickness of 415 μm, surface roughness of <1 μm, and sufficient flexibility was extruded continuously at a rate of 10 m/min., but it required a more traditional coat hanger manifold to prevent filler hang up in the sheet die. The filler particles were distributed uniformly through the core and skin of the sheet, giving the sheet good mechanical properties.