Hydroxytyrosol targets extracellular matrix remodeling by endothelial cells and inhibits both ex vivo and in vivo angiogenesis

This is the preprint version of our manuscript, corresponding to the article that has been 
published in final form at FOOD CHEMISTRY with DOI: 10.1016/j.foodchem.2016.10.111The health benefits of olive oil are attributed to their bioactive compounds, such as hydroxytyrosol. Previously, we demonstrated that hydroxytyrosol inhibits angiogenesis in vitro. The present study aimed to: i) get further insight into the effects of hydroxytyrosol on extracellular matrix remodeling; and ii) test whether hydroxytyrosol is able to inhibit angiogenesis ex vivo and in vivo. Hydroxytyrosol induced a shift toward inhibition of proteolysis in endothelial cells, with decreased expression of extracellular matrix remodeling-enzyme coding genes and increased levels of some of their inhibitors. Furthermore, this work demonstrated that hydroxytyrosol, at concentrations within the range of its content in virgin olive oil that can be absorbed from moderate and sustained virgin olive oil consumption, is a strong inhibitor of angiogenesis ex vivo and in vivo. These results suggest the need for translational studies to evaluate the potential use of hydroxytyrosol for angio-prevention and angiogenesis inhibition in clinical setting.This work was supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER). The “CIBER de Enfermedades Raras” is an initiative from the ISCIII (Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript

Do plants adjust their sex allocation and secondary sexual morphology in response to their neighbours?

Background and aims Changes in the sex allocation (i.e. in pollen versus seed production) of hermaphroditic plants often occur in response to the environment. In some homosporous ferns, gametophytes choose their gender in response to chemical cues sent by neighbours, such that spores develop as male gametophytes if they perceive a female or hermaphrodite nearby. Here it is considered whether a similar process might occur in the androdioecious angiosperm species Mercurialis annua, in which males co-occur with hermaphrodites; previous work on a Spanish population of M. annua found that individuals were more likely to develop as males at high density. Methods Using a novel approach to treat plants with leachate from pots containing males or hermaphrodites of M. annua, the hypothesis that individuals assess their mating opportunities, and adjust their sex expression accordingly, was tested through an exchange of chemical cues through the soil. Key Results For the population under study, from Morocco, no evidence was found for soil-signal-dependent sex expression: neither sex ratios nor sex allocation differed among experimental treatments. Conclusions The results imply either that the Moroccan population under study behaves differently from that previously studied in Spain (pointing to potential geographical variation in plasticity for sex expression), or that our method failed to capture the signals used by M. annua for adjustment of sex expressio

Are biases towards the recent past causing us to unintentionally expose personnel to increased levels of risk?

PresentationThis paper focuses on the consideration of an unbiased approach to assessing risk to push the industry towards proactively addressing risk rather than reactively allowing cognitive biases to drive process safety culture and personnel risk management solutions. Scientifically proven to affect the way we process and interpret the world around us, cognitive biases allow us to shortcut the complexities of the world when making decisions. In some cases, biases can be surprisingly accurate, while in other instances they can lead to making poor judgements and decisions based on the limited information available to us. Specifically damaging in the process safety industry are the availability heuristic and the confirmation bias, which together cause us to focus on information that comes to mind quickly, justifies our opinions, and favors our existing beliefs. With recent industrial accidents that have resulted in fatalities and a push toward regulatory change in response to explosion events, we have seen a rise in the availability of blast resistant structures such as BRMs and hardened stick-built buildings to protect onsite personnel from explosions. The availability of such blast hardened structures has produced an unfortunate trend of moving personnel back in closer to processing areas. Recent advancements in full-scale testing and computer modeling capabilities suggests that even though such buildings may protect for some level of blast hazards, this approach may result in increased levels of personnel risk from other hazard types, specifically impinged jet fires and toxic exposure. This raises the question: are employees being placed in risky locations in a BRM or hardened building with a false sense of security

Active inference as a computational framework for consciousness

Recently, the mechanistic framework of active inference has been put forward as a principled foundation to develop an overarching theory of consciousness which would help address conceptual disparities in the field (Wiese 2018; Hohwy and Seth 2020). For that promise to bear out, we argue that current proposals resting on the active inference scheme need refinement to become a process theory of consciousness. One way of improving a theory in mechanistic terms is to use formalisms such as computational models that implement, attune and validate the conceptual notions put forward. Here, we examine how computational modelling approaches have been used to refine the theoretical proposals linking active inference and consciousness, with a focus on the extent and success to which they have been developed to accommodate different facets of consciousness and experimental paradigms, as well as how simulations and empirical data have been used to test and improve these computational models. While current attempts using this approach have shown promising results, we argue they remain preliminary in nature. To refine their predictive and structural validity, testing those models against empirical data is needed i.e., new and unobserved neural data. A remaining challenge for active inference to become a theory of consciousness is to generalize the model to accommodate the broad range of consciousness explananda; and in particular to account for the phenomenological aspects of experience. Notwithstanding these gaps, this approach has proven to be a valuable avenue for theory advancement and holds great potential for future research

The noni anthraquinone damnacanthal is a multi-kinase inhibitor with potent anti-angiogenic effects

Este es el manuscrito que fue aceptado y que finalmente se publicó en Cancer Letters con el DOI: 10.1016/j.canlet.2016.10.037The natural bioactive compound damnacanthal inhibits several tyrosine kinases. Herein, we show that -in fact- damancanthal is a multi kinase inhibitor. A docking and molecular dynamics simulation approach allows getting further insight on the inhibitory effect of damnacanthal on three different kinases: vascular endothelial growth factor receptor-2, c-Met and focal adhesion kinase. Several of the kinases targeted and inhibited by damnacanthal are involved in angiogenesis. Ex vivo and in vivo experiments clearly demonstrate that, indeed, damnacanthal is a very potent inhibitor of angiogenesis. A number of in vitro assays contribute to determine the specific effects of damnacanthal on each of the steps of the angiogenic process, including inhibition of tubulogenesis, endothelial cell proliferation, survival, migration and production of extracellular matrix remodeling enzyme. Taken altogether, these results suggest that damancanthal could have potential interest for the treatment of cancer and other angiogenesisdependent diseases.Supported by grants BIO2014-56092-R (MINECO and FEDER), P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). JAGV had the financial support of Vicerrectorado de Investigación y Transferencia (University of Málaga, Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript

Beeswax foundations with impregnated thymol for Varroa control

The use of essential oils and organic acids is generally accepted as an alternative tool for the control of the Varroa Destructor levels in bee's colonies, avoiding mite resistance and reducing the residues contaminations resulting from the systematic application of synthetic chemicals

Family therapy interventions for psychopathy

Research into developmental aspects of antisocial behaviour and psychopathy has made strong progress in recent decades. The findings most notably informed by growing evidence regarding callous-unemotional (CU) traits suggest that the neurodevelopmental abnormalities associated with psychopathy emerge early in life, and are shaped by genetics, biology, and environmental factors. In line with this, initial trials of intervention programs for antisocial youth with CU traits have begun to show the potential for family-based interventions to reduce antisocial behaviour as well as CU traits when delivered early in life. Importantly, this research also suggests family interventions may need to be adapted to meet the unique needs of high CU youth. This chapter reviews current best approaches to adapting family interventions for antisocial youth with CU traits. We further argue that it is timely to examine the integration of current theories of antisocial behaviour with emerging scientific frameworks for personalizing clinical intervention. Three core issues are discussed in accordance with scientific frameworks for personalizing interventions relevant to adapting family interventions for high CU youth: (i) research supporting family interventions as an evidence supported treatment for antisocial behaviour as the primary problem (ii) research supporting family-based interventions as the best model of intervention for antisocial youth with CU traits, and (iii) putative treatment strategies that may be integrated or adapted for family interventions such that programs are tailored to the unique developmental aspects of antisocial behaviour among high CU youth. An evaluation of promising best-treatment approach(es) is discussed as well as future directions for research