Metabolomic Analysis of the Effect of Postnatal Hypoxia on the Retina in a Newly Born Piglet Model

The availability of reliable biomarkers of brain injury secondary to birth asphyxia could substantially improve clinical grading, therapeutic intervention strategies, and prognosis. In this study, changes in the metabolome of retinal tissue caused by profound hypoxia in an established neonatal piglet model were investigated using an ultra performance liquid chromatography – quadrupole time of flight mass spectrometry (UPLC-QTOFMS) untargeted metabolomic approach, which included Partial Least Squares – Discriminant Analysis (PLSDA) multivariate data analysis. The initial identification of a set of discriminant metabolites from UPLC-QTOFMS data was confirmed by target UPLC-MS/MS and allowed the selection of endogenous CDP-choline as a promising candidate biomarker for hypoxia-derived brain damage assessing intensity of retinal hypoxia. Results from this study will foster further research on CDP-choline changes occurring during resuscitation.     

New Insights on Cytological and Metabolic Features of Ostreopsis cf. ovata Fukuyo (Dinophyceae): A Multidisciplinary Approach

The harmful dinoflagellate Ostreopsis cf. ovata has been causing toxic events along the Mediterranean coasts and other temperate and tropical areas, with increasing frequency during the last decade. Despite many studies, important biological features of this species are still poorly known. An integrated study, using different microscopy and molecular techniques, Raman microspectroscopy and high resolution liquid chromatography-mass spectrometry (HR LC-MS), was undertaken to elucidate cytological aspects, and identify main metabolites including toxins. The species was genetically identified as O. cf. ovata, Atlantic-Mediterranean clade. The ultrastructural results show unique features of the mucilage network abundantly produced by this species to colonize benthic substrates, with a new role of trichocysts, never described before. The amorphous polysaccharidic component of mucilage appears to derive from pusule fibrous material and mucocysts. In all stages of growth, the cells show an abundant production of lipids. Different developmental stages of chloroplasts are found in the peripheral cytoplasm and in the centre of cell. In vivo Raman microspectroscopy confirms the presence of the carotenoid peridinin in O. cf. ovata, and detects in several specimen the abundant presence of unsaturated lipids structurally related to docosahexaenoic acid. The HR LC-MS analysis reveals that ovatoxin-a is the predominant toxin, together with decreasing amounts of ovatoxin-b, -d/e, -c and putative palytoxin. Toxins concentration on a per cell basis increases from exponential to senescent phase. The results suggest that benthic blooms of this species are probably related to features such as the ability to create a unique mucilaginous sheath covering the sea bottom, associated with the production of potent toxins as palytoxin-like compounds. In this way, O. cf. ovata may be able to rapidly colonize benthic substrates outcompeting other species.     

New variants in Spanish Niemann–Pick type c disease patients

Molecular Biology Reports - Niemann–Pick type C (NPC) disease is a rare inherited disease, with progressive neurodegeneration as the main symptom. It is a lysosomal storage disorder caused by...     

The impact of thermal seasonality on terrestrial endotherm food web dynamics: a revision of the Exploitation Ecosystem Hypothesis

Many terrestrial endotherm food webs constitute three trophic level cascades. Others have two trophic level dynamics (food limited herbivores; plants adapted to tackle intense herbivory) or one trophic level dynamic (herbivorous endotherms absent, thus plants compete for the few places where they can survive and grow). According to the Exploitation Ecosystems Hypothesis (EEH), these contrasting dynamics are consequences of differences in primary productivity. The productivity thresholds for changing food web dynamics were assumed to be global constants. We challenged this assumption and found that several model parameters are sensitive to the contrast between persistently warm and seasonally cold climates. In persistently warm environments, three trophic level dynamics can be expected to prevail almost everywhere, save the most extreme deserts. We revised EEH accordingly and tested it by compiling direct evidence of three and two trophic level dynamics and by studying the global distribution of felids. In seasonally cold environments, we found evidence for three trophic level dynamics only in productive ecosystems, while evidence for two trophic level dynamics appeared in ecosystems with low primary productivity. In persistently warm environments, we found evidence for three trophic level dynamics in all types of ecosystems. The distribution of felids corroborated these results. The empirical evidence thus indicates that two trophic level dynamics, as defined by EEH, are restricted to seasonally cold biomes with low primary productivity, such as the artic–alpine tundra and the temperate steppe.     

Uni-molecular detection and quantification of selected β-lactam antibiotics with a hybrid α-hemolysin protein pore

Single-nanopores have recently been used to electrically detect a wide range of analytes. Similarly, using electrophysiology, we demonstrate how a system comprised of an ion channel formed by α-hemolysin (α-HL) and single-cyclic γ-cyclodextrin (γ-CD) molecule permits the detection of, and differentiation between three different antibiotics from the β-lactam family. Specifically, histograms of the time between the successive binding events, and the residence time distributions of the antibiotic in the γ-CD molecular adapter vary with the antibiotic type. The results show that the association times of amoxicillin, azlocillin, and ampicillin are τ(on) = 2.1 ± 0.2, 2.2 ± 0.3, and 3.1 ± 0.4 ms, respectively. Interestingly, we found that the residence time of the bulkier and negatively charged azlocillin (τ(off) = 0.008 ± 0.0005 ms) is much less than that of ampicillin (τ(off) = 0.07 ± 0.005 ms) and amoxicillin (τ(off) = 0.1 ± 0.02 ms), even though the γ-CD-α-HL complex is anionic selective. The data were also used to estimate the standard free energy of binding between ampicillin to γ-CDs binding (-12 kJ mol(-1) [corrected]). The difference in association times might be due to γ-CDs-imposed steric hindrance or an energetically more expensive desolvation step for the antibiotics to gain access to the binding site in the CD. We suggest that this technique may be used to detect other analytes used in pharmaceutical applications.     

Topical anti-inflammatory activity of boropinic acid and its natural and semi-synthetic derivatives

Boropinic acid is a natural isopentenyloxycinnamic acid extracted from the aerial parts of Boronia pinnata Sm. (Rutaceae) with soybean 5-lipoxygenase inhibitory activity. In this paper the topical anti-inflammatory activity of boropinic acid and some of its natural and semi-synthetic derivatives was evaluated using the Croton oil ear test in mice as a model of acute inflammation. Some of the tested compounds (15, 17, 19, 20) revealed an effect comparable (ID₅₀ = 0.18 ÷ 0.72 μmol/cm²) to that of the reference drug indomethacin (ID₅₀ = 0.23 μmol/cm²), a non-steroidal anti-inflammatory drug.     

Variation of trabecular architecture in proximal femur of postmenopausal women

This investigation of microstructure in the human proximal femur probes the relationship between the parameters of the FRAX index of fracture risk and the parameters of bone microstructure. The specificity of fracture sites at the proximal femur raises the question of whether trabecular parameters are site-specific during post-menopause, before occurrence of fragility fracture. The donated proximal femurs of sixteen post-menopausal women in the sixth and seventh decades of life, free of metabolic pathologies and therapeutic interventions that could have altered the bone tissue, constituted the material of the study. We assessed bone mineral density of the proximal femurs by dual energy X-ray absorptiometry and then sectioned the femurs through the center of the femoral head and along the femoral neck axis. For each proximal femur, morphometry of trabeculae was conducted on the plane of the section divided into conventional regions and sub-regions consistent with the previously identified trabecular families that provide regions of relatively homogeneous microstructure. Mean trabecular width and percent bone area were calculated at such sites. Our findings indicate that each of mean trabecular width and percent bone area vary within each proximal femur independently from each other, with dependence on site. Both trabecular parameters show significant differences between pairs of sites. We speculate that a high FRAX index at the hip corresponds to a reduced percent bone area among sites that gives a more homogeneous and less site-specific quality to the proximal femur. This phenomenon may render the local tissue less able to carry out the expected mechanical function.     

Little evidence of a road‐effect zone for nocturnal,flying insects

Roads and traffic may be contributing to global declines of insect populations. The ecological effects of roads often extend far into the surrounding habitat, over a distance known as the road‐effect zone. The quality of habitat in the road‐effect zone is generally degraded (e.g., due to edge effects, noise, light, and chemical pollution) and can be reflected in species presence, abundance, or demographic parameters. Road‐effect zones have been quantified for some vertebrate species but are yet to be quantified for insects. Investigating the road‐effect zone for insects will provide a better understanding of how roads impact ecosystems, which is particularly important given the role insects play as pollinators, predators, and prey for other species. We quantified the road‐effect zone for nocturnal flying insects along three major freeways in agricultural landscapes in southeast Australia. We collected insects using light traps at six points along 2‐km transects perpendicular to each highway (n = 17). We sorted the samples into order, and dried and weighed each order to obtain a measure of dry biomass. Using regression models within a Bayesian framework of inference, we estimated the change in biomass of each order with distance from the road, while accounting for environmental variables such as temperature, moon phase, and vegetation structure. The biomass of nine of the ten orders sampled did not change with distance from the freeway. Orthoptera (i.e., grasshoppers and crickets) was the only order whose biomass increased with distance from the freeway. From our findings, we suggest that the impacts of roads on insects are unlikely extending into the surrounding landscape over a distance of 2 km. Therefore, if there are impacts of roads on insects, these are more likely to be concentrated at the road itself, or on finer taxonomic scales such as family or genus level.