New perspectives on bioactivity of olive oil: evidence from animal models, human interventions and the use of urinary proteomic biomarkers

Olive oil (OO) is the primary source of fat in the Mediterranean diet and has been associated with longevity and a lower incidence of chronic diseases, particularly CHD. Cardioprotective effects of OO consumption have been widely related with improved lipoprotein profile, endothelial function and inflammation, linked to health claims of oleic acid and phenolic content of OO. With CVD being a leading cause of death worldwide, a review of the potential mechanisms underpinning the impact of OO in the prevention of disease is warranted. The current body of evidence relies on mechanistic studies involving animal and cell-based models, epidemiological studies of OO intake and risk factor, small- and large-scale human interventions, and the emerging use of novel biomarker techniques associated with disease risk. Although model systems are important for mechanistic research nutrition, methodologies and experimental designs with strong translational value are still lacking. The present review critically appraises the available evidence to date, with particular focus on emerging novel biomarkers for disease risk assessment. New perspectives on OO research are outlined, especially those with scope to clarify key mechanisms by which OO consumption exerts health benefits. The use of urinary proteomic biomarkers, as highly specific disease biomarkers, is highlighted towards a higher translational approach involving OO in nutritional recommendations

Osmotic stress induces JNK-dependent embryo invasion in a model of implantation

In vitro culture during assisted reproduction technologies (ARTs) exposes pre-implantation embryos to environmental stressors, such as non-physiological nutritional, oxidative and osmotic conditions. The effects on subsequent implantation are not well understood but could contribute to poor ART efficiency and outcomes. We have used exposure to hyperosmolarity to investigate the effects of stress on the ability of embryos to interact with endometrial cells in an in vitro model. Culturing mouse blastocysts for 2 h in medium with osmolarity raised by 400 mosmol induced blastocoel collapse and re-expansion, but did not affect subsequent attachment to, or invasion of, the endometrial epithelial Ishikawa cell line. Inhibition of stress-responsive c-Jun N-terminal kinase (JNK) activity with SP600125 did not affect the intercellular interactions between these embryos and the epithelial cells. Four successive cycles of hyperosmotic stress at E5.5 had no effect on attachment, but promoted embryonic breaching of the epithelial cell layer by trophoblast giant cells in a JNK-dependent manner. These findings suggest that acute stress at the blastocyst stage may promote trophoblast breaching of the endometrial epithelium at implantation and implicates stress signalling through JNK in the process of trophectoderm differentiation into the invasive trophoblast necessary for the establishment of pregnancy. The data may lead to increased understanding of factors governing ART success rates and safety

Apposition to endometrial epithelial cells activates mouse blastocysts for implantation.

How do interactions between blastocyst-stage embryos and endometrial epithelial cells regulate the early stages of implantation in an in vitro model?Mouse blastocyst apposition with human endometrial epithelial cells initiates trophectoderm differentiation to trophoblast, which goes on to breach the endometrial epithelium.In vitro models using mouse blastocysts and human endometrial cell lines have proven invaluable in the molecular characterisation of embryo attachment to endometrial epithelium at the onset of implantation. Genes involved in embryonic breaching of the endometrial epithelium have not been investigated in such in vitro models.This study used an established in vitro model of implantation to examine cellular and molecular interactions during blastocyst attachment to endometrial epithelial cells.Mouse blastocysts developed from embryonic day (E) 1.5 in vitro were hatched and co-cultured with confluent human endometrial adenocarcinoma-derived Ishikawa cells in serum-free medium. A scale of attachment stability based on blastocyst oscillation upon agitation was devised. Blastocysts were monitored for 48 h to establish the kinetics of implantation, and optical sectioning using fluorescence microscopy revealed attachment and invasion interfaces. Quantitative PCR was used to determine blastocyst gene expression. Data from a total of 680 mouse blastocysts are reported, with 3-6 experimental replicates. T-test and ANOVA analyses established statistical significance at P < 0.05, P < 0.01 and P < 0.001.Hatched E4.5 mouse blastocysts exhibited weak attachment to confluent Ishikawa cells over the first 24 h of co-culture, with intermediate and stable attachment occurring from 28 h (E5.5 + 4 h) in a hormone-independent manner. Attached embryos fixed after 48 h (E6.5) frequently exhibited outgrowths, characterised morphologically and with antibody markers as trophoblast giant cells (TGCs), which had breached the Ishikawa cell layer. Beginning co-culture at E5.5 also resulted in intermediate and stable attachment from E5.5 + 4 h; however, these embryos did not go on to breach the Ishikawa cell layer, even when co-culture was extended to E7.5 (P < 0.01). Blastocysts cultured from E4.5 in permeable transwell inserts above Ishikawa cells before transfer to direct co-culture at E5.5 went on to attach but failed to breach the Ishikawa cell layer by E6.5 (P < 0.01). Gene expression analysis at E5.5 demonstrated that direct co-culture with Ishikawa cells from E4.5 resulted in downregulation of trophectoderm transcription factors Cdx2 (P < 0.05) and Gata3 (P < 0.05) and upregulation of the TGC transcription factor Hand1 (P < 0.05). Co-culture with non-endometrial human fibroblasts did not alter the expression of these genes.None.The in vitro model used here combines human carcinoma-derived endometrial cells with mouse embryos, in which the cellular interactions observed may not fully recapitulate those in vivo. The data gleaned from such models can be regarded as hypothesis-generating, and research is now needed to develop more sophisticated models of human implantation combining multiple primary endometrial cell types with surrogate and real human embryos.This study implicates blastocyst apposition to endometrial epithelial cells as a critical step in trophoblast differentiation required for implantation. Understanding this maternal regulation of the embryonic developmental programme may lead to novel treatments for infertility.This work was supported by funds from the charities Wellbeing of Women (RG1442) and Diabetes UK (15/0005207), and studentship support for SCB from the Anatomical Society. No conflict of interest is declared

First Results on In-Beam gamma Spectroscopy of Neutron-Rich Na and Mg Isotopes at REX-ISOLDE

After the successful commissioning of the radioactive beam experiment at ISOLDE (REX-ISOLDE) - an accelerator for exotic nuclei produced by ISOLDE - first physics experiments using these beams were performed. Initial experiments focused on the region of deformation in the vicinity of the neutron-rich Na and Mg isotopes. Preliminary results show the high potential and physics opportunities offered by the exotic isotope accelerator REX in conjunction with the modern Germanium gamma spectrometer MINIBALL.Comment: 7 pages, RNB6 conference contributio

Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells

Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.Peer reviewe

New perspectives on bioactivity of olive oil: evidence from animal models, human interventions and the use of urinary proteomic biomarkers

Olive oil (OO) is the primary source of fat in the Mediterranean diet and has been associated with longevity and a lower incidence of chronic diseases, particularly CHD. Cardioprotective effects of OO consumption have been widely related with improved lipoprotein profile, endothelial function and inflammation, linked to health claims of oleic acid and phenolic content of OO. With CVD being a leading cause of death worldwide, a review of the potential mechanisms underpinning the impact of OO in the prevention of disease is warranted. The current body of evidence relies on mechanistic studies involving animal and cell-based models, epidemiological studies of OO intake and risk factor, small- and large-scale human interventions, and the emerging use of novel biomarker techniques associated with disease risk. Although model systems are important for mechanistic research nutrition, methodologies and experimental designs with strong translational value are still lacking. The present review critically appraises the available evidence to date, with particular focus on emerging novel biomarkers for disease risk assessment. New perspectives on OO research are outlined, especially those with scope to clarify key mechanisms by which OO consumption exerts health benefits. The use of urinary proteomic biomarkers, as highly specific disease biomarkers, is highlighted towards a higher translational approach involving OO in nutritional recommendations

Film as architectural theory

Publications on architectural theory have predominantly taken on the form of text-based books, monographs, and articles. With the rise of transdisciplinary and practice-based research in architecture, new opportunities are opening up for other forms of architectural theory, such as film-based mediums, which promise to expand and alter the convention of the written practice of theory. Two possible types of filmic theory are presented here. One follows the method of ethnographic documentary filmmaking inspired by Sarah Pinkfilm-based mediums, which promise to expand and alter thellows the line of art house filmmaking inspired by Kathryn Rameyyn Rameyg inspired by Sarah Pinkfilm-based mediums, which promise to expand ae to expand ad mediums, which promise to expand a convention of the written practice of theory. or constructing knowledge, new discourses on filmic theory can be opened up. It is argued here that film as architectural theory is part of this new discourse, broadening the audience’u engagement with architecture through not only “readership” but also “viewership.

Mycobacterium tuberculosis Complex Mycobacteria as Amoeba-Resistant Organisms

International audienceBackground: Most environmental non-tuberculous mycobacteria have been demonstrated to invade amoebal trophozoites and cysts, but such relationships are largely unknown for members of the Mycobacterium tuberculosis complex. An environmental source has been proposed for the animal Mycobacterium bovis and the human Mycobacterium canettii.Methodology/Principal Findings: Using optic and electron microscopy and co-culture methods, we observed that 89±0.6% of M. canettii, 12.4±0.3% of M. tuberculosis, 11.7±2% of M. bovis and 11.2±0.5% of Mycobacterium avium control organisms were phagocytized by Acanthamoeba polyphaga, a ratio significantly higher for M. canettii (P = 0.03), correlating with the significantly larger size of M. canetti organisms (P = 0.035). The percentage of intraamoebal mycobacteria surviving into cytoplasmic vacuoles was 32±2% for M. canettii, 26±1% for M. tuberculosis, 28±2% for M. bovis and 36±2% for M. avium (P = 0.57). M. tuberculosis, M. bovis and M. avium mycobacteria were further entrapped within the double wall of <1% amoebal cysts, but no M. canettii organisms were observed in amoebal cysts. The number of intracystic mycobacteria was significantly (P = 10−6) higher for M. avium than for the M. tuberculosis complex, and sub-culturing intracystic mycobacteria yielded significantly more (P = 0.02) M. avium organisms (34×104 CFU/mL) than M. tuberculosis (42×101 CFU/mL) and M. bovis (35×101 CFU/mL) in the presence of a washing fluid free of mycobacteria. Mycobacteria survived in the cysts for up to 18 days and cysts protected M. tuberculosis organisms against mycobactericidal 5 mg/mL streptomycin and 2.5% glutaraldehyde.Conclusions/Significance: These data indicate that M. tuberculosis complex organisms are amoeba-resistant organisms, as previously demonstrated for non-tuberculous, environmental mycobacteria. Intercystic survival of tuberculous mycobacteria, except for M. canettii, protect them against biocides and could play a role in their life cycle

Thermal stratification drives movement of a coastal apex predator

A characterization of the thermal ecology of fishes is needed to better understand changes in ecosystems and species distributions arising from global warming. The movement of wild animals during changing environmental conditions provides essential information to help predict the future thermal response of large marine predators. We used acoustic telemetry to monitor the vertical movement activity of the common dentex (Dentex dentex), a Mediterranean coastal predator, in relation to the oscillations of the seasonal thermocline during two summer periods in the Medes Islands marine reserve (NW Mediterranean Sea). During the summer stratification period, the common dentex presented a clear preference for the warm suprathermoclinal layer, and adjusted their vertical movements following the depth changes of the thermocline. The same preference was also observed during the night, when fish were less active. Due to this behaviour, we hypothesize that inter-annual thermal oscillations and the predicted lengthening of summer conditions will have a significant positive impact on the metabolic efficiency, activity levels, and population dynamics of this species, particularly in its northern limit of distribution. These changes in the dynamics of an ecosystem’s keystone predator might cascade down to lower trophic levels, potentially re-defining the coastal fish communities of the futureVersión del editor2,92