A hierarchical algorithm for predicting the linear viscoelastic properties of polymer melts with long-chain branching

The “hierarchical model” proposed earlier [Larson in Macromolecules 34:4556–4571, 2001] is herein modified by inclusion of early time fluctuations and other refinements drawn from the theories of Milner and McLeish for more quantitative prediction. The hierarchical model predictions are then compared with experimental linear viscoelastic data of well-defined long chain branched 1,4-polybutadienes and 1,4-polyisoprenes using a single set of parameter values for each polymer, which are obtained from experimental data for monodisperse linear and star polymers. For a wide range of monodisperse branched polymer melts, the predictions of the hierarchical model for monodisperse melts are very similar to those of the Milner–McLeish theories, and agree well with experimental data for many, but not all, of the branched polymer samples. Since the modified hierarchical model accounts for arbitrary polydispersity in molecular weight and branching distributions, which is not accounted for in the Milner–McLeish theories, the hierarchical algorithm is a promising one for predicting the relaxation of general mixtures of branched polymers.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47217/1/397_2004_Article_415.pd

Does dietary tocopherol level affect fatty acid metabolism in fish?

Fish are a rich source of the n-3 polyunsaturated fatty acids (PUFA), particularly the highly unsaturated fatty acids (HUFA), eicosapentaenoic (EPA; 20:5n-3) and docosahexaenoic (DHA; 22:6n-3) acids, which are vital constituents for cell membrane structure and function, but which are also highly susceptible to attack by oxygen and other organic radicals. Resultant damage to PUFA in membrane phospholipids can have serious consequences for cell membrane structure and function, with potential pathological effects on cells and tissues. Physiological antioxidant protection involves both endogenous components, such as free radical scavenging enzymes, and exogenous dietary micronutrients including tocopherols and tocotrienols, the vitamin E-type compounds, widely regarded as the primary lipid soluble antioxidants. The antioxidant activities of tocopherols are imparted by their ability to donate their phenolic hydrogen atoms to lipid (fatty acid) free radicals resulting in the stabilisation of the latter and the termination of the lipid peroxidation chain reaction. However, tocopherols can also prevent PUFA peroxidation by acting as quenchers of singlet oxygen. Recent studies on marine fish have shown correlations between dietary and tissue PUFA/tocopherol ratios and incidence of lipid peroxidation as indicated by the levels of TBARS and isoprostanes. These studies also showed that feeding diets containing oxidised oil significantly affected the activities of liver antioxidant defence enzymes and that dietary tocopherol partially attenuated these effects. However, there is evidence that dietary tocopherols can affect fatty acid metabolism in other ways. An increase in membrane PUFA was observed in rats deficient in vitamin E. This was suggested to be due to over production of PUFA arising from increased activity of the desaturation/elongation mechanisms responsible for the synthesis of PUFA. Consistent with this, increased desaturation of 18:3n-3 and 20:5n-3 in hepatocytes from salmon fed diets deficient in tocopherol and/or astaxanthin has been observed. Although the mechanism is unclear, tocopherols may influence biosynthesis of n-3PUFA through alteration of cellular oxidation potential or “peroxide tone”

Challenge clusters facing LCA in environmental decision-making—what we can learn from biofuels

Purpose Bioenergy is increasingly used to help meet greenhouse gas (GHG) and renewable energy targets. However, bioenergy’s sustainability has been questioned, resulting in increasing use of life cycle assessment (LCA). Bioenergy systems are global and complex, and market forces can result in significant changes, relevant to LCA and policy. The goal of this paper is to illustrate the complexities associated with LCA, with particular focus on bioenergy and associated policy development, so that its use can more effectively inform policymakers. Methods The review is based on the results from a series of workshops focused on bioenergy life cycle assessment. Expert submissions were compiled and categorized within the first two workshops. Over 100 issues emerged. Accounting for redundancies and close similarities in the list, this reduced to around 60 challenges, many of which are deeply interrelated. Some of these issues were then explored further at a policyfacing workshop in London, UK. The authors applied a rigorous approach to categorize the challenges identified to be at the intersection of biofuels/bioenergy LCA and policy. Results and discussion The credibility of LCA is core to its use in policy. Even LCAs that comply with ISO standards and policy and regulatory instruments leave a great deal of scope for interpretation and flexibility. Within the bioenergy sector, this has led to frustration and at times a lack of obvious direction. This paper identifies the main challenge clusters: overarching issues, application and practice and value and ethical judgments. Many of these are reflective of the transition from application of LCA to assess individual products or systems to the wider approach that is becoming more common. Uncertainty in impact assessment strongly influences planning and compliance due to challenges in assigning accountability, and communicating the inherent complexity and uncertainty within bioenergy is becoming of greater importance. Conclusions The emergence of LCA in bioenergy governance is particularly significant because other sectors are likely to transition to similar governance models. LCA is being stretched to accommodate complex and broad policy-relevant questions, seeking to incorporate externalities that have major implications for long-term sustainability. As policy increasingly relies on LCA, the strains placed on the methodology are becoming both clearer and impedimentary. The implications for energy policy, and in particular bioenergy, are large

Nck adapter proteins: functional versatility in T cells

Nck is a ubiquitously expressed adapter protein that is almost exclusively built of one SH2 domain and three SH3 domains. The two isoproteins of Nck are functionally redundant in many aspects and differ in only few amino acids that are mostly located in the linker regions between the interaction modules. Nck proteins connect receptor and non-receptor tyrosine kinases to the machinery of actin reorganisation. Thereby, Nck regulates activation-dependent processes during cell polarisation and migration and plays a crucial role in the signal transduction of a variety of receptors including for instance PDGF-, HGF-, VEGF- and Ephrin receptors. In most cases, the SH2 domain mediates binding to the phosphorylated receptor or associated phosphoproteins, while SH3 domain interactions lead to the formation of larger protein complexes. In T lymphocytes, Nck plays a pivotal role in the T cell receptor (TCR)-induced reorganisation of the actin cytoskeleton and the formation of the immunological synapse. However, in this context, two different mechanisms and adapter complexes are discussed. In the first scenario, dependent on an activation-induced conformational change in the CD3ε subunits, a direct binding of Nck to components of the TCR/CD3 complex was shown. In the second scenario, Nck is recruited to the TCR complex via phosphorylated Slp76, another central constituent of the membrane proximal activation complex. Over the past years, a large number of putative Nck interactors have been identified in different cellular systems that point to diverse additional functions of the adapter protein, e.g. in the control of gene expression and proliferation

Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

CD36 and Fyn kinase mediate malaria-induced lung endothelial barrier dysfunction in mice infected with Plasmodium berghei.

PMC3744507Severe malaria can trigger acute lung injury characterized by pulmonary edema resulting from increased endothelial permeability. However, the mechanism through which lung fluid conductance is altered during malaria remains unclear. To define the role that the scavenger receptor CD36 may play in mediating this response, C57BL/6J (WT) and CD36-/- mice were infected with P. berghei ANKA and monitored for changes in pulmonary endothelial barrier function employing an isolated perfused lung system. WT lungs demonstrated a >10-fold increase in two measures of paracellular fluid conductance and a decrease in the albumin reflection coefficient (σalb) compared to control lungs indicating a loss of barrier function. In contrast, malaria-infected CD36-/- mice had near normal fluid conductance but a similar reduction in σalb. In WT mice, lung sequestered iRBCs demonstrated production of reactive oxygen species (ROS). To determine whether knockout of CD36 could protect against ROS-induced endothelial barrier dysfunction, mouse lung microvascular endothelial monolayers (MLMVEC) from WT and CD36-/- mice were exposed to H2O2. Unlike WT monolayers, which showed dose-dependent decreases in transendothelial electrical resistance (TER) from H2O2 indicating loss of barrier function, CD36-/- MLMVEC demonstrated dose-dependent increases in TER. The differences between responses in WT and CD36-/- endothelial cells correlated with important differences in the intracellular compartmentalization of the CD36-associated Fyn kinase. Malaria infection increased total lung Fyn levels in CD36-/- lungs compared to WT, but this increase was due to elevated production of the inactive form of Fyn further suggesting a dysregulation of Fyn-mediated signaling. The importance of Fyn in CD36-dependent endothelial signaling was confirmed using in vitro Fyn knockdown as well as Fyn-/- mice, which were also protected from H2O2- and malaria-induced lung endothelial leak, respectively. Our results demonstrate that CD36 and Fyn kinase are critical mediators of the increased lung endothelial fluid conductance caused by malaria infection.JH Libraries Open Access Fun