The effect of curvature and topology on membrane hydrodynamics

We study the mobility of extended objects (rods) on a spherical liquid-liquid interface to show how this quantity is modified in a striking manner by both the curvature and the topology of the interface. We present theoretical calculations and experimental measurements of the interfacial fluid velocity field around a moving rod bound to the crowded interface of a water-in-oil droplet. By using different droplet sizes, membrane viscosities, and rod lengths, we show that the viscosity mismatch between the interior and exterior fluids leads to a suppression of the fluid flow on small droplets that cannot be captured by the flat interface predictions.Comment: 4 pages, 3 figure

Polyelectrolyte Bundles

Using extensive Molecular Dynamics simulations we study the behavior of polyelectrolytes with hydrophobic side chains, which are known to form cylindrical micelles in aqueous solution. We investigate the stability of such bundles with respect to hydrophobicity, the strength of the electrostatic interaction, and the bundle size. We show that for the parameter range relevant for sulfonated poly-para-phenylenes (PPP) one finds a stable finite bundle size. In a more generic model we also show the influence of the length of the precursor oligomer on the stability of the bundles. We also point out that our model has close similarities to DNA solutions with added condensing agents, hinting to the possibility that the size of DNA aggregates is under certain circumstances thermodynamically limited.Comment: 10 pages, 8 figure

Genus expansion for real Wishart matrices

We present an exact formula for moments and cumulants of several real compound Wishart matrices in terms of an Euler characteristic expansion, similar to the genus expansion for complex random matrices. We consider their asymptotic values in the large matrix limit: as in a genus expansion, the terms which survive in the large matrix limit are those with the greatest Euler characteristic, that is, either spheres or collections of spheres. This topological construction motivates an algebraic expression for the moments and cumulants in terms of the symmetric group. We examine the combinatorial properties distinguishing the leading order terms. By considering higher cumulants, we give a central limit-type theorem for the asymptotic distribution around the expected value

In Vitro Evaluation of the Toxicological Profile and Oxidative Stress of Relevant Diet-Related Advanced Glycation End Products and Related 1,2-Dicarbonyls

During food processing and storage, and in tissues and fluids under physiological conditions, the Maillard reaction occurs. During this reaction, reactive 1,2-dicarbonyl compounds arise as intermediates that undergo further reactions to form advanced glycation end products (AGEs). Diet is the primary source of exogenous AGEs. Endogenously formed AGEs have been proposed as a risk factor in the pathogenesis of diet-related diseases such as diabetes, insulin resistance, cardiovascular diseases, or chronic disease. AGEs may differently contribute to the diet-related exacerbation of oxidative stress, inflammation, and protein modifications. Here, to understand the contribution of each compound, we tested individually, for the first time, the effect of five 1,2-dicarbonyl compounds 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 3,4-dideoxyglucosone-3-ene (3,4-DGE), glyoxal (GO), and methylglyoxal (MGO) and four different glycated amino acids N-ε-(carboxyethyl)lysine (CEL), N-ε-(carboxymethyl)lysine (CML), methylglyoxal-derived hydroimidazolone-1 (MG-H1), and pyrraline (Pyrr) in a cell line of human keratinocytes (HaCaT). We found that most of the glycated amino acids, i.e., CEL, CML, and MG-H1, did not show any cytotoxicity. At the same time, 1,2-dicarbonyl compounds 3-DGal, 3,4-DGE, GO, and MGO increased the production of reactive oxygen species and induced cell death. MGO induced cell death by apoptosis, whereas 3-DGal and 3,4-DGE induced nuclear translocation of the proinflammatory NF-κB transcription pathway, and the activation of the pyroptosis-related NLRP3 inflammasome cascade. Overall, these results demonstrate the higher toxic impact of 1,2-dicarbonyl compounds on mucosal epithelial cells when compared to glycated amino acids and the selective activation of intracellular signaling pathways involved in the crosstalk mechanisms linking oxidative stress to excessive inflammation

Effective Viscosity of a Dilute Suspension of Membrane-bound Inclusions

When particulate suspensions are sheared, perturbations in the shear flows around the rigid particles increase the local energy dissipation, so that the viscosity of the suspension is effectively higher than that of the solvent. For bulk (three-dimensional) fluids, understanding this viscosity enhancement is a classic problem in hydrodynamics that originated over a century ago with Einstein's study of a dilute suspension of spherical particles. \cite{Einstein1} In this paper, we investigate the analogous problem of the effective viscosity of a suspension of disks embedded in a two-dimensional membrane or interface. Unlike the hydrodynamics of bulk fluids, low-Reynolds number membrane hydrodynamics is characterized by an inherent length scale generated by the coupling of the membrane to the bulk fluids that surround it. As a result, we find that the size of the particles in the suspension relative to this hydrodynamic length scale has a dramatic effect on the effective viscosity of the suspension. Our study also helps to elucidate the mathematical tools needed to solve the mixed boundary value problems that generically arise when considering the motion of rigid inclusions in fluid membranes.Comment: 33 pages, 4 figures (preprint); submitted to Physics of Fluid

Biodiversity conservation across scales: lessons from a science–policy dialogue

One of the core challenges of biodiversity conservation is to better understand the interconnectedness and interactions of scales in ecological and governance processes. These interrelationships constitute not only a complex analytical challenge but they also open up a channel for deliberative discussions and knowledge exchange between and among various societal actors which may themselves be operating at various scales, such as policy makers, land use planners, members of NGOs, and researchers. In this paper, we discuss and integrate the perspectives of various disciplines academics and stakeholders who participated in a workshop on scales of European biodiversity governance organised in Brussels in the autumn of 2010. The 23 participants represented various governmental agencies and NGOs from the European, national, and sub-national levels. The data from the focus group discussions of the workshop were analysed using qualitative content analysis. The core scale-related challenges of biodiversity policy identified by the participants were cross-level and cross-sector limitations as well as ecological, social and social-ecological complexities that potentially lead to a variety of scale-related mismatches. As ways to address these cha- llenges the participants highlighted innovations, and an aim to develop new interdisciplinary approaches to support the processes aiming to solve current scale challenges

Cytokine and immunoglobulin production by PWM-stimulated peripheral and tumor-infiltrating lymphocytes of undifferentiated nasopharyngeal carcinoma (NPC) patients

BACKGROUND: Undifferentiated Nasopharyngeal Carcinoma (NPC) patients show a characteristic pattern of antibody responses to the Epstein-Barr virus (EBV) which is regularly associated with this tumor. However, no EBV-specific cytotoxic activity is detectable by the standard chromium-release assay at both peripheral and intratumoral levels. The mechanisms underlying this discrepancy between the humoral and cellular immune responses in NPC are still unknown, but might be related to an imbalance in immunoregulatory interleukin production. In this report, we investigated the ability of peripheral (PBL) and tumor- infiltrating (TIL) lymphocytes of undifferentiated NPC patients to produce in vitro three interleukins (IL-2, IL-6, IL-10) and three immunoglobulin isotypes (IgM, IgG, IgA). METHODS: Lymphocytes from 17 patients and 17 controls were cultured in the presence of Pokeweed mitogen (PWM) for 12 days and their culture supernatants were tested for interleukins and immunoglobulins by specific enzyme-linked immunosorbent assays (ELISA). Data were analysed using Student's t-test and probability values below 5% were considered significant. RESULTS: The data obtained indicated that TIL of NPC patients produced significantly more IL-2 (p = 0,0002), IL-10 (p = 0,020), IgM (p= 0,0003) and IgG (p < 0,0001) than their PBL. On the other hand, patients PBL produced significantly higher levels of IL-2 (p = 0,022), IL-10 (p = 0,016) and IgM (p = 0,004) than those of controls. No significant differences for IL-6 and IgA were observed. CONCLUSION: Taken together, our data reinforce the possibility of an imbalance in immunoregulatory interleukin production in NPC patients. An increased ability to produce cytokines such as IL-10 may underlie the discrepancy between humoral and cellular immune responses characteristic of NPC

Presence of Epstein-Barr virus latency type III at the single cell level in post- transplantation lymphoproliferative disorders and AIDS related lymphomas

AIMS: To investigate the expression pattern of Epstein-Barr virus (EBV) latent genes at the single cell level in post-transplantation lymphoproliferative disorders and acquired immunodefiency syndrome (AIDS) related lymphomas, in relation to cellular morphology. METHODS: Nine post-transplantation lymphoproliferative disorders and three AIDS related lymphomas were subjected to immunohistochemistry using monoclonal antibodies specific for EBV nuclear antigen 1 (EBNA1) (2H4), EBNA2 (PE2 and the new rat anti-EBNA2 monoclonal antibodies 1E6, R3, and 3E9), and LMP1 (CS1-4 and S12). Double staining was performed combining R3 or 3E9 with S12. RESULTS: R3 and 3E9 anti-EBNA2 monoclonal antibodies were more sensitive than PE2, enabling the detection of more EBNA2 positive lymphoma cells. Both in post-transplantation lymphoproliferative disorders and AIDS related lymphomas, different expression patterns were detected at the single cell level. Smaller neoplastic cells were positive for EBNA2 but negative for LMP1. Larger and more blastic neoplastic cells, sometimes resembling Reed-Sternberg cells, were LMP1 positive but EBNA2 negative (EBV latency type II). Morphologically intermediate neoplastic cells coexpressing EBNA2 and LMP1 (EBV latency type III), were detected using R3 and 3E9, and formed a considerable part of the neoplastic population in four of nine post-transplantation lymphoproliferative disorders and two of three AIDS related lymphomas. All samples contained a subpopulation of small tumour cells positive exclusively for Epstein-Barr early RNA and EBNA1. The relation between cellular morphology and EBV expression patterns in this study was less pronounced in AIDS related lymphomas than in post-transplantation lymphoproliferative disorders, because the AIDS related lymphomas were less polymorphic than the post-transplantation lymphoproliferative disorders. CONCLUSIONS: In post-transplantation lymphoproliferative disorders and AIDS related lymphomas, EBV latency type III can be detected by immunohistochemistry in a subpopulation of tumour cells using sensitive monoclonal antibodies R3 and 3E9. Our data suggest that EBV infected tumour cells in these lymphomas undergo gradual changes in the expression of EBV latent genes, and that these changes are associated with changes in cellular morphology