Nutrient Uptake by a Deposit-Feeding Enteropneust: Nitrogenous Sources

We measured carbon, nitrogen, protein, bacterial and microalgal abundance, and mineral-specific surface area in sediments from the feeding zone of undisturbed Saccoglossus kowalewskyi, as well as in their fresh egesta. Comparison of results using surficial material 1 mm) and the top 3 mm of sediments indicated ingestion of surficial material by the enteropneusts. Assuming the surficial sediment as a food source results in apparent absorption efficiencies of 15% for TOC, 35% for TON, 60% for protein and 86% for microalgae. The C:N ratio of the apparently absorbed material was 4.2, consistent with an amino acid-rich diet. Protein- nitrogen uptake, however, accounted for only about 28% of total nitrogen absorption, indicating a dominant use of non-protein nitrogen . Bacterial and microalgal contributions to dietary nitrogen uptake were no more than 3% and 4% respectively. Active worms maintain 2 foraging areas with an average total foraging volume of 0.9 cm3 and a volume ingestion rate of 0.06 to 0.12 cm3 ind.-1 h-1. If the preferred feeding zone of these enteropneusts is the nitrogen -enriched surficial layer, we estimate that their feeding activities will deplete the available food resources every 8 to 16 h and they may rely on biological and tidal redistribution of surface material

Effects of phosphatidylserine on membrane incorporation and surface protection properties of exchangeable poly(ethylene glycol)-conjugated lipids

AbstractLiposomes containing the acidic phospholipid phosphatidylserine (PS) have been shown to avidly interact with proteins involved in blood coagulation and complement activation. Membranes with PS were therefore used to assess the shielding properties of poly(ethylene glycol 2000)-derivatized phosphatidylethanolamine (PE-PEG2000) with various acyl chain lengths on membranes containing reactive lipids. The desorption of PE-PEG2000 from PS containing liposomes was studied using an in vitro assay which involved the transfer of PE-PEG2000 into multilamellar vesicles, and the reactivity of PS containing liposomes was monitored by quantifying interactions with blood coagulation proteins. The percent inhibition of clotting activity of PS liposomes was dependent on the PE-PEG2000 content. 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-PEG2000 which transferred out slowly from PS liposomes was able to abolish >80% of clotting activity of PS liposomes at 15 mol%. This level of DSPE-PEG2000 was also able to extend the mean residence time of PS liposomes from 0.2 h to 14 h. However, PE-PEG2000 with shorter acyl chains such as 1,2-dimyristyl-sn-glycero-3-phosphoethanolamine-PEG2000 were rapidly transferred out from PS liposomes, which resulted in a 73% decrease in clotting activity inhibition and 45% of administered intravenously liposomes were removed from the blood within 15 min after injection. Thus, PS facilitates the desorption of PE-PEG2000 from PS containing liposomes, thereby providing additional control of PEG release rates from membrane surfaces. These results suggest that membrane reactivity can be selectively regulated by surface grafted PEGs coupled to phosphatidylethanolamine of an appropriate acyl chain length

Intermembrane transfer of polyethylene glycol-modified phosphatidylethanolamine as a means to reveal surface-associated binding ligands on liposomes

AbstractIn order to explore the use of exchangeable poly(ethylene glycol) (PEG)-modified diacylphosphatidylethanolamines (PE) to temporarily shield binding ligands attached to the surface of liposomes, a model reaction based on inhibition and subsequent recovery of biotinylated liposome binding to streptavidin immobilized on superparamagnetic iron oxide particles (SA magnetic particles) was developed. PEG-lipid incorporation into biotinylated liposomes decreased liposome binding to SA magnetic particles in a non-linear fashion, where as little as 0.1 mol% PEG-PE resulted in a 20% decrease in binding. Using an assay based on inhibition of binding, PEG2000-PE transfer from donor liposomes to biotinylated acceptor liposomes could be measured. The influence of temperature and acyl chain composition on the transfer of PEG-diacyl PEs from donor liposomes to acceptor liposomes, consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine, cholesterol and N-((6-biotinoyl)amino)hexanoyl)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (54.9:45:0.1 mole ratio), was measured. Donor liposomes were prepared using 1,2-distearoyl-sn-glycero-3-phosphocholine (50 mol%), cholesterol (45 mol%) and 5 mol% of either PEG-derivatized 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE-PEG2000), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE-PEG2000), or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE-PEG2000). Transfer of DSPE-PEG2000 to the donor liposomes was not detected under the conditions employed. In contrast, DMPE-PEG2000 was transferred efficiently even at 4°C. Using an acceptor to donor liposome ratio of 1:4, the time required for DMPE-PEG2000 to become evenly distributed between the two liposome populations (TEQ) at 4°C and 37°C was approx. 2 and <0.5 h, respectively. An increase in acyl chain length from C14:0 to C16:0 of the PEG-lipid resulted in a significant reduction in the rate of transfer as measured by this assay. The transfer of PEG-lipid out of biotinylated liposomes was also studied in mice following intravenous administration. The relative rates of transfer for the various PEG-lipids were found to be comparable under in vivo and in vitro conditions. These results suggest that it is possible to design targeted liposomes with the targeting ligand protected while in the circulation through the use of PEG-lipids that are selected on the basis of exchange characteristics which result in exposure of the shielded ligand following localization within a target tissue

Reflection on modern methods: constructing directed acyclic graphs (DAGs) with domain experts for health services research

Directed acyclic graphs (DAGs) are a useful tool to represent, in a graphical format, researchers’ assumptions about the causal structure among variables while providing a rationale for the choice of confounding variables to adjust for. With origins in the field of probabilistic graphical modelling, DAGs are yet to be widely adopted in applied health research, where causal assumptions are frequently made for the purpose of evaluating health services initiatives. In this context, there is still limited practical guidance on how to construct and use DAGs. Some progress has recently been made in terms of building DAGs based on studies from the literature, but an area that has received less attention is how to create DAGs from information provided by domain experts, an approach of particular importance when there is limited published information about the intervention under study. This approach offers the opportunity for findings to be more robust and relevant to patients, carers and the public, and more likely to inform policy and clinical practice. This article draws lessons from a stakeholder workshop involving patients, health care professionals, researchers, commissioners and representatives from industry, whose objective was to draw DAGs for a complex intervention—online consultation, i.e. written exchange between the patient and health care professional using an online system—in the context of the English National Health Service. We provide some initial, practical guidance to those interested in engaging with domain experts to develop DAGs

Coencapsulation of irinotecan and floxuridine into low cholesterol-containing liposomes that coordinate drug release in vivo

AbstractA liposomal delivery system that coordinates the release of irinotecan and floxuridine in vivo has been developed. The encapsulation of floxuridine was achieved through passive entrapment while irinotecan was actively loaded using a novel copper gluconate/triethanolamine based procedure. Coordinating the release rates of both drugs was achieved by altering the cholesterol content of distearoylphosphatidylcholine (DSPC)/distearoylphosphatidylglycerol (DSPG) based formulations. The liposomal retention of floxuridine in plasma after intravenous injection was dramatically improved by decreasing the cholesterol content of the formulation below 20 mol%. In the case of irinotecan, the opposite trend was observed where increasing cholesterol content enhanced drug retention. Liposomes composed of DSPC/DSPG/Chol (7:2:1, mole ratio) containing co-encapsulated irinotecan and floxuridine at a 1:1 molar ratio exhibited matched leakage rates for the two agents so that the 1:1 ratio was maintained after intravenous administration to mice. The encapsulation of irinotecan was optimal when copper gluconate/triethanolamine (pH 7.4) was used as the intraliposomal buffer. The efficiency of irinotecan loading was approximately 80% with a starting drug to lipid molar ratio of 0.1/1. Leakage of floxuridine from the liposomes during irinotecan loading at 50 °C complicated the ability to readily achieve the target 1:1 irinotecan/floxuridine ratio inside the formulation. As a result, a procedure for the simultaneous encapsulation of irinotecan and floxuridine was developed. This co-encapsulation method has the advantage over sequential loading in that extrusion can be performed in the absence of chemotherapeutic agents and the drug/drug ratios in the final formulation can be more precisely controlled

Preparing for a Northwest Passage: A Workshop on the Role of New England in Navigating the New Arctic

Preparing for a Northwest Passage: A Workshop on the Role of New England in Navigating the New Arctic (March 25 - 27, 2018 -- The University of New Hampshire) paired two of NSF\u27s 10 Big Ideas: Navigating the New Arctic and Growing Convergence Research at NSF. During this event, participants assessed economic, environmental, and social impacts of Arctic change on New England and established convergence research initiatives to prepare for, adapt to, and respond to these effects. Shipping routes through an ice-free Northwest Passage in combination with modifications to ocean circulation and regional climate patterns linked to Arctic ice melt will affect trade, fisheries, tourism, coastal ecology, air and water quality, animal migration, and demographics not only in the Arctic but also in lower latitude coastal regions such as New England. With profound changes on the horizon, this is a critical opportunity for New England to prepare for uncertain yet inevitable economic and environmental impacts of Arctic change

Topological mirror symmetry with fluxes

Motivated by SU(3) structure compactifications, we show explicitly how to construct half--flat topological mirrors to Calabi--Yau manifolds with NS fluxes. Units of flux are exchanged with torsion factors in the cohomology of the mirror; this is the topological complement of previous differential--geometric mirror rules. The construction modifies explicit SYZ fibrations for compact Calabi--Yaus. The results are of independent interest for SU(3) compactifications. For example one can exhibit explicitly which massive forms should be used for Kaluza--Klein reduction, proving previous conjectures. Formality shows that these forms carry no topological information; this is also confirmed by infrared limits and old classification theorems.Comment: 35 pages, 5 figure

Factors influencing time to case registration for youth with type 1 and type 2 diabetes: SEARCH for Diabetes in Youth Study

The development of a sustainable pediatric diabetes surveillance system for the United States requires a better understanding of issues related to case ascertainment

Fructose intake and cardiovascular risk factors in youth with type 1 diabetes: SEARCH for diabetes in youth study

High consumption of dietary fructose has been shown to contribute to dyslipidemia and elevated blood pressure in adults, but there are few data in youth, particularly those at greater risk of cardiovascular disease (CVD). The aim of this study was to examine the association between fructose intake and CVD risk factors in a diverse population of youth with type 1diabetes (T1D)