Light-Activated Liposomes Coated with Hyaluronic Acid as a Potential Drug Delivery System

Light-activated liposomes permit site and time-specific drug delivery to ocular and systemic targets. We combined a light activation technology based on indocyanine green with a hyaluronic acid (HA) coating by synthesizing HA–lipid conjugates. HA is an endogenous vitreal polysaccharide and a potential targeting moiety to cluster of differentiation 44 (CD44)-expressing cells. Light-activated drug release from 100 nm HA-coated liposomes was functional in buffer, plasma, and vitreous samples. The HA-coating improved stability in plasma compared to polyethylene glycol (PEG)-coated liposomes. Liposomal protein coronas on HA- and PEG-coated liposomes after dynamic exposure to undiluted human plasma and porcine vitreous samples were hydrophilic and negatively charged, thicker in plasma (~5 nm hard, ~10 nm soft coronas) than in vitreous (~2 nm hard, ~3 nm soft coronas) samples. Their compositions were dependent on liposome formulation and surface charge in plasma but not in vitreous samples. Compared to the PEG coating, the HA-coated liposomes bound more proteins in vitreous samples and enriched proteins related to collagen interactions, possibly explaining their slightly reduced vitreal mobility. The properties of the most abundant proteins did not correlate with liposome size or charge, but included proteins with surfactant and immune system functions in plasma and vitreous samples. The HA-coated light-activated liposomes are a functional and promising alternative for intravenous and ocular drug delivery

Spatial structure of the 8200 cal yr BP event in northern Europe

International audienceA synthesis of well-dated high-resolution pollen records suggests a spatial structure in the 8200 cal yr BP event in northern Europe. The temperate, thermophilous tree taxa, especially Corylus, Ulmus, and Alnus, decline abruptly between 8300 and 8000 cal yr BP at most sites located south of 61° N, whereas there is no clear change in pollen values at the sites located in the North-European tree-line region. Pollen-based quantitative temperature reconstructions and several other, independent palaeoclimate proxies, such as lacustrine oxygen-isotope records, reflect the same pattern, with no detectable cooling in the sub-arctic region. The observed patterns challenges the general view of the wide-spread occurrence of the 8200 cal yr BP event in the North Atlantic region. An alternative explanation is that the cooling during the 8200 cal yr BP event took place mostly during the winter and spring, and the ecosystems in the south responded sensitively to the cooling during the onset of the growing season. In contrast, in the sub-arctic area, where the vegetation was still dormant and lakes ice-covered, the cold event is not reflected in pollen-based or lake-sediment-based records

Review of the Commission Decision 2010/477/EU concerning MSFD criteria for assessing Good Environmental Status, Descriptor 7

This report represents the result of the scientific and technical review of Commission Decision 2010/477/EU in relation to Descriptor 7. The review has been carried out by the EC JRC together with experts nominated by EU Member States, and has considered contributions from the GES Working Group in accordance with the roadmap set out in the MSFD implementation strategy (agreed on at the 11th CIS MSCG meeting). The report is one of a series of reports (review manuals) including Descriptor 1, 2, 5, 7, 8, 9, 10 that conclude phase 1 of the review process and, as agreed within the MSFD Common Implementation Strategy, are the basis for review phase 2, towards an eventual revision of the Commission Decision 2010/477/EU. The report presents the state of the technical discussions as of 30 April 2015 (document version 7.0: ComDecRev_D7_V7.0_FINAL.docx), as some discussions are ongoing, it does not contain agreed conclusions on all issues. The document does not represent an official, formal position of any of the Member States and the views expressed in the document are not to be taken as representing the views of the European Commission.JRC.H.1-Water Resource

Paternal Diet Defines Offspring Chromatin State and Intergenerational Obesity

The global rise in obesity has revitalized a search for genetic and epigenetic factors underlying the disease. We present a Drosophila model of paternal-diet-induced intergenerational metabolic reprogramming (IGMR) and identify genes required for its encoding in offspring. Intriguingly, we find that as little as 2 days of dietary intervention in fathers elicits obesity in offspring. Paternal sugar acts as a physiological suppressor of variegation, desilencing chromatin-state-defined domains in both mature sperm and in offspring embryos. We identify requirements for H3K9/K27me3-dependent reprogramming of metabolic genes in two distinct germline and zygotic windows. Critically, we find evidence that a similar system may regulate obesity susceptibility and phenotype variation in mice and humans. The findings provide insight into the mechanisms underlying intergenerational metabolic reprogramming and carry profound implications for our understanding of phenotypic variation and evolution

Species and habitats in danger : estimating the relative risk posed by oil spills in the northern Baltic Sea

Large-scale oil spills can have adverse effects on biodiversity in coastal areas where maritime oil transportation is intense. In this article we conducted a spatial risk assessment to study the risk that potential tanker accidents pose to threatened habitat types and species living in the northern Baltic Sea, which has witnessed a rapid increase in maritime oil transportation within the past two decades. We applied a probabilistic method, which combines three components: a Bayesian network describing tanker accidents and uncertainties related to them, probabilistic maps showing the movement of oil, and a database of threatened species and habitats in the area. The results suggest that spatial risk posed by oil spills varies across the area, and does not correspond, for example, to the frequency of accidents in a given area. The relative risk is highest for seashore meadows, which is important to take into account when managing these habitats. Our analysis underlines the importance of a thorough risk assessment, which is not only based solely on one or two specific factors such as accident probabilities or the trajectories of spilled oil but also contains as broad a view of the consequences as possible. We believe that the probabilistic methodology applied in the study will be of high interest to people who have to cope with uncertainties typical for environmental risk assessment and management.Peer reviewe

Assessment of Forest Biomass and Carbon Stocks at Stand Level Using Site-Specific Primary Data to Support Forest Management

To quantify and map woody biomass (WB) and forest carbon (C) stocks, several models were developed. They differ in terms of scale of application, details related to the input data required and outputs provided. Local Authorities, such as Mountain Communities, can be supported in sustainable forest planning and management by providing specific models in which the reference unit is the same as the one reported in the Forest Management Plans (FMP), i.e. the forest stand. In the Lombardy Region (Northern Italy), a few studies were performed to assess WB and forest C stocks, and they were generally based on data coming from regional\u2014or national\u2014forest inventories and remote sensing, without taking into account data collected in the FMPs. For this study, the first version of the stand-level model \u201cWOody biomass and Carbon ASsessment\u201d (WOCAS) for WB and C stocks calculation was improved into a second version (WOCAS v2) and preliminary results about its first application to 2019 forest stands of Valle Camonica District (Lombardy Region) are presented. Since the model WOCAS uses the growing stock as the main driver for the calculation, it can be applied in any other forest area where the same input data are available

The biology of inequalities in health: The LIFEPATH project

Socioeconomic differences in health have been consistently observed worldwide. Physical health deteriorates more rapidly with age among men and women with lower socioeconomic status (SES) than among those with higher SES. The biological processes underlying these differences are best understood by adopting a life course approach. In this paper we introduce the pan- European LIFEPATH project which uses multiple cohorts - including biomarker data - to investigate ageing as a phenomenon with two broad stages across life: build-up and decline. The ‘build-up’ stage, from conception and early intra-uterine life to late adolescence or early twenties, is characterised by rapid successions of developmentally and socially sensitive periods. The second stage, starting in early adulthood, is a period of ‘decline’ from maximum attained health to loss of function, overt disease and death. LIFEPATH adopts a study design that integrates social science and public health approaches with biology (including molecular epidemiology), using well-characterised population cohorts and omics measurements (particularly epigenomics). LIFEPATH includes information and biological samples from 17 cohorts, including several with extensive phenotyping and repeat biological samples, and a very large cohort (1 million individuals) without biological samples (WHIP, from Italy). The countries that are covered by the cohorts are France, Italy, Portugal, Ireland, UK, Finland, Switzerland and Australia. These cohorts are only a small proportion of all cohorts available in Europe, but we have chosen them for the combination of good measures of socioeconomic status, risk factors for non-communicable diseases (NCDs) and biomarkers already measured (or availability of blood samples for further testing). The majority of cohorts include ‘hard’ outcomes (diabetes, cancer, Cardiovascular Disease (CVD), total mortality), and the extensively phenotyped cohorts also include several measurements of the functional components of healthy ageing, including frailty, impaired vision, cognitive function, renal and brain function, osteoporosis, sleep disturbances and mental health. All age groups are represented with two birth cohorts, one cohort of adolescents and several cohorts encompassing young adults (age 18 and above). Furthermore, there is a strong representation of elderly subjects in seven cohorts. The specific objectives of the project are: (a) to show that healthy ageing is an achievable goal for society; (b) to improve the understanding of the mechanisms through which healthy ageing pathways diverge by SES, by investigating life course biological pathways using omic technologies; (c) to examine the consequences of the current economic recession on health and the biology of ageing (and the consequent increase in social inequalities); (d) to provide updated, relevant and innovative evidence for healthy ageing policies (particularly ‘health in all policies’) using both observational studies and an experimental approach based on a reanalysis of data from a ‘conditional cash transfer’ randomised experiment in New York and new data collected as part of an earned income tax credit randomised experiment in Atlanta and New York. To achieve these objectives, data are used from three categories of studies: 1. national census-based followup data to obtain mortality by socioeconomic status; 2. cohorts with intense phenotyping and repeat biological samples; 3. large cohorts with biological samples. With these objectives and methodologies, LIFEPATH seeks to provide updated, relevant and innovative evidence to underpin future policies and strategies for the promotion of healthy ageing, targeted disease prevention and clinical interventions that address the issue of social disparities in ageing and the social determinants of health. The present paper describes the design and some initial results of LIFEPATH as an example of the integration of social and biological sciences to provide evidence for public health policies

Allostatic load and subsequent all-cause mortality: which biological markers drive the relationship? Findings from a UK birth cohort

The concept of allostatic load (AL) refers to the idea of a global physiological ‘wear and tear’ resulting from the adaptation to the environment through the stress response systems over the life span. The link between socioeconomic position (SEP) and mortality has now been established, and there is evidence that AL may capture the link between SEP and mortality. In order to quantitatively assess the role of AL on mortality, we use data from the 1958 British birth cohort including eleven year mortality in 8,113 adults. Specifically, we interrogate the hypothesis of a cumulative biological risk (allostatic load) reflecting 4 physiological systems potentially predicting future risk of death (N = 132). AL was defined using 14 biomarkers assayed in blood from a biosample collected at 44 years of age. Cox proportional hazard regression analysis revealed that higher allostatic load at 44 years old was a significant predictor of mortality 11 years later [HR = 3.56 (2.3 to 5.53)]. We found that this relationship was not solely related to early-life SEP, adverse childhood experiences and young adulthood health status, behaviours and SEP [HR = 2.57 (1.59 to 4.15)] . Regarding the ability of each physiological system and biomarkers to predict future death, our results suggest that the cumulative measure was advantageous compared to evaluating each physiological system sub-score and biomarker separately. Our findings add some evidence of a biological embodiment in response to stress which ultimately affects mortality

Combinatorial Activation and Repression by Seven Transcription Factors Specify Drosophila Odorant Receptor Expression

A systematic analysis reveals a regulatory network controlling selective odorant receptor expression and neuronal diversity in Drosophila