Emergence of structural and dynamical properties of ecological mutualistic networks

Mutualistic networks are formed when the interactions between two classes of species are mutually beneficial. They are important examples of cooperation shaped by evolution. Mutualism between animals and plants plays a key role in the organization of ecological communities. Such networks in ecology have generically evolved a nested architecture independent of species composition and latitude - specialists interact with proper subsets of the nodes with whom generalists interact. Despite sustained efforts to explain observed network structure on the basis of community-level stability or persistence, such correlative studies have reached minimal consensus. Here we demonstrate that nested interaction networks could emerge as a consequence of an optimization principle aimed at maximizing the species abundance in mutualistic communities. Using analytical and numerical approaches, we show that because of the mutualistic interactions, an increase in abundance of a given species results in a corresponding increase in the total number of individuals in the community, as also the nestedness of the interaction matrix. Indeed, the species abundances and the nestedness of the interaction matrix are correlated by an amount that depends on the strength of the mutualistic interactions. Nestedness and the observed spontaneous emergence of generalist and specialist species occur for several dynamical implementations of the variational principle under stationary conditions. Optimized networks, while remaining stable, tend to be less resilient than their counterparts with randomly assigned interactions. In particular, we analytically show that the abundance of the rarest species is directly linked to the resilience of the community. Our work provides a unifying framework for studying the emergent structural and dynamical properties of ecological mutualistic networks.Comment: 10 pages, 4 figure

Effects of rotation and thermohaline mixing in red giant stars

Thermohaline mixing has been recently identified as the probable dominating process that governs the photospheric composition of low-mass bright giant stars. Here we present the predictions of stellar models computed with the code STAREVOL including this mechanism together with rotational mixing. We compare our theoretical predictions with recent observations.Comment: Proc. of the workshop "Red Giants as Probes of the Structure and Evolution of the Milky Way" (Roma, 15-17 Nov 2010), Astrophysics and Space Science Proceedings, ISBN 978-3-642-18417-8 (eds. A. Miglio, J. Montalban, A. Noels). Part of RedGiantsMilkyWay/2011/ proceedings available at http://arxiv.org/html/1108.4406v

A review of gene-drug interactions for nonsteroidal anti-inflammatory drug use in preventing colorectal neoplasia.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective chemopreventive agents for colorectal neoplasia. Polymorphisms in NSAID targets or metabolizing enzymes may affect NSAID efficacy or toxicity. We conducted a literature review to summarize current evidence of gene-drug interactions between NSAID use and polymorphisms in COX1, COX2, ODC, UGT1A6 and CYP2C9 on risk of colorectal neoplasia by searching OVID and PubMed. Of 134 relevant search results, thirteen investigated an interaction. One study reported a significant interaction between NSAID use and the COX1 Pro17Leu polymorphism (P=0.03) whereby the risk reduction associated with NSAID use among homozygous wild-type genotypes was not observed among NSAID users with variant alleles. Recent pharmacodynamic data support the potential for gene-drug interactions for COX1 Pro17Leu. Statistically significant interactions have also been reported for ODC (315G>A), UGT1A6 (Thr181Ala+Arg184Ser or Arg184Ser alone), and CYP2C9 (*2/*3). No statistically significant interactions have been reported for polymorphisms in COX2; however, an interaction with COX2 -765G>C approached significance (P=0.07) in one study. Among seven remaining studies, reported interactions were not statistically significant for COX1, COX2 and ODC gene polymorphisms. Most studies were of limited sample size. Definitions of NSAID use differed substantially between studies. The literature on NSAID-gene interactions to date is limited. Reliable detection of gene-NSAID interactions will require greater sample sizes, consistent definitions of NSAID use and evaluation of clinical trial subjects of chemoprevention studies

Treatment options for severe hypertriglyceridemia (SHTG): the role of apheresis

Hypertriglyceridemia is associated with a number of severe diseases such as acute pancreatitis and coronary artery disease. In severe hypertriglyceridemia (SHTG, triglycerides > 1,000 mg/dL), rapid lowering of plasma triglycerides (TG) has to be achieved. Treatment regimes include nutritional intervention, the use of antihyperlipidemic drugs, and therapeutic apheresis. Apheretic treatment is indicated in medical emergencies such as hypertriglyceridemic pancreatitis

Mice Doubly-Deficient in Lysosomal Hexosaminidase A and Neuraminidase 4 Show Epileptic Crises and Rapid Neuronal Loss

Tay-Sachs disease is a severe lysosomal disorder caused by mutations in the HexA gene coding for the α-subunit of lysosomal β-hexosaminidase A, which converts GM2 to GM3 ganglioside. Hexa−/− mice, depleted of β-hexosaminidase A, remain asymptomatic to 1 year of age, because they catabolise GM2 ganglioside via a lysosomal sialidase into glycolipid GA2, which is further processed by β-hexosaminidase B to lactosyl-ceramide, thereby bypassing the β-hexosaminidase A defect. Since this bypass is not effective in humans, infantile Tay-Sachs disease is fatal in the first years of life. Previously, we identified a novel ganglioside metabolizing sialidase, Neu4, abundantly expressed in mouse brain neurons. Now we demonstrate that mice with targeted disruption of both Neu4 and Hexa genes (Neu4−/−;Hexa−/−) show epileptic seizures with 40% penetrance correlating with polyspike discharges on the cortical electrodes of the electroencephalogram. Single knockout Hexa−/− or Neu4−/− siblings do not show such symptoms. Further, double-knockout but not single-knockout mice have multiple degenerating neurons in the cortex and hippocampus and multiple layers of cortical neurons accumulating GM2 ganglioside. Together, our data suggest that the Neu4 block exacerbates the disease in Hexa−/− mice, indicating that Neu4 is a modifier gene in the mouse model of Tay-Sachs disease, reducing the disease severity through the metabolic bypass. However, while disease severity in the double mutant is increased, it is not profound suggesting that Neu4 is not the only sialidase contributing to the metabolic bypass in Hexa−/− mice

Differential expression of Lp-PLA2 in obesity and type 2 diabetes and the influence of lipids

Aims/hypothesis Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulatory macrophage-derived factor that increases with obesity and leads to a higher risk of cardiovascular disease (CVD). Despite this, its role in adipose tissue and the adipocyte is unknown. Therefore, the aims of this study were to clarify the expression of Lp-PLA2 in relation to different adipose tissue depots and type 2 diabetes, and ascertain whether markers of obesity and type 2 diabetes correlate with circulating Lp-PLA2. A final aim was to evaluate the effect of cholesterol on cellular Lp-PLA2 in an in vitro adipocyte model. Methods Analysis of anthropometric and biochemical variables from a cohort of lean (age 44.4 ± 6.2 years; BMI 22.15 ± 1.8 kg/m2, n = 23), overweight (age 45.4 ± 12.3 years; BMI 26.99 ± 1.5 kg/m2, n = 24), obese (age 49.0 ± 9.1 years; BMI 33.74 ± 3.3 kg/m2, n = 32) and type 2 diabetic women (age 53.0 ± 6.13 years; BMI 35.08 ± 8.6 kg/m2, n = 35), as part of an ethically approved study. Gene and protein expression of PLA2 and its isoforms were assessed in adipose tissue samples, with serum analysis undertaken to assess circulating Lp-PLA2 and its association with cardiometabolic risk markers. A human adipocyte cell model, Chub-S7, was used to address the intracellular change in Lp-PLA2 in adipocytes. Results Lp-PLA2 and calcium-independent PLA2 (iPLA2) isoforms were altered by adiposity, as shown by microarray analysis (p < 0.05). Type 2 diabetes status was also observed to significantly alter gene and protein levels of Lp-PLA2 in abdominal subcutaneous (AbdSc) (p < 0.01), but not omental, adipose tissue. Furthermore, multivariate stepwise regression analysis of circulating Lp-PLA2 and metabolic markers revealed that the greatest predictor of Lp-PLA2 in non-diabetic individuals was LDL-cholesterol (p = 0.004). Additionally, in people with type 2 diabetes, oxidised LDL (oxLDL), triacylglycerols and HDL-cholesterol appeared important predictors, accounting for 59.7% of the variance (p < 0.001). Subsequent in vitro studies determined human adipocytes to be a source of Lp-PLA2, as confirmed by mRNA expression, protein levels and immunochemistry. Further in vitro experiments revealed that treatment with LDL-cholesterol or oxLDL resulted in significant upregulation of Lp-PLA2, while inhibition of Lp-PLA2 reduced oxLDL production by 19.8% (p < 0.05). Conclusions/interpretation Our study suggests adipose tissue and adipocytes are active sources of Lp-PLA2, with differential regulation by fat depot and metabolic state. Moreover, levels of circulating Lp-PLA2 appear to be influenced by unfavourable lipid profiles in type 2 diabetes, which may occur in part through regulation of LDL-cholesterol and oxLDL metabolism in adipocytes

Paradoxes and Mechanisms for Choice under Risk

Experiments on choice under risk typically involve multiple decisions by individual subjects. The choice of mechanism for selecting decision(s) for payoff is an essential design feature unless subjects isolate each one of the multiple decisions. We report treatments with different payoff mechanisms but the same decision tasks. The data show large differences across mechanisms in subjects’ revealed risk preferences, a clear violation of isolation. We illustrate the importance of these mechanism effects by identifying their implications for classical tests of theories of decision under risk. We discuss theoretical properties of commonly used mechanisms, and new mechanisms introduced herein, in order to clarify which mechanisms are theoretically incentive compatible for which theories. We identify behavioral properties of some mechanisms that can introduce bias in elicited risk preferences – from cross-task contamination – even when the mechanism used is theoretically incentive compatible. We explain that selection of a payoff mechanism is an important component of experimental design in many topic areas including social preferences, public goods, bargaining, and choice under uncertainty and ambiguity as well as experiments on decisions under risk

Analysis of Polymorphisms and Haplotype Structure of the Human Thymidylate Synthase Genetic Region: A Tool for Pharmacogenetic Studies

5-fluorouracil (5FU), a widely used chemotherapeutic drug, inhibits the DNA replicative enzyme, thymidylate synthase (Tyms). Prior studies implicated a VNTR (variable numbers of tandem repeats) polymorphism in the 5′-untranslated region (5′-UTR) of the TYMS gene as a determinant of Tyms expression in tumors and normal tissues and proposed that these VNTR genotypes could help decide fluoropyrimidine dosing. Clinical associations between 5FU-related toxicity and the TYMS VNTR were reported, however, results were inconsistent, suggesting that additional genetic variation in the TYMS gene might influence Tyms expression. We thus conducted a detailed genetic analysis of this region, defining new polymorphisms in this gene including mononucleotide (poly A:T) repeats and novel single nucleotide polymorphisms (SNPs) flanking the VNTR in the TYMS genetic region. Our haplotype analysis of this region used data from both established and novel genetic variants and found nine SNP haplotypes accounting for more than 90% of the studied population. We observed non-exclusive relationships between the VNTR and adjacent SNP haplotypes, such that each type of VNTR commonly occurred on several haplotype backgrounds. Our results confirmed the expectation that the VNTR alleles exhibit homoplasy and lack the common ancestry required for a reliable marker of a linked adjacent locus that might govern toxicity. We propose that it may be necessary in a clinical trial to assay multiple types of genetic polymorphisms in the TYMS region to meaningfully model linkage of genetic markers to 5FU-related toxicity. The presence of multiple long (up to 26 nt), polymorphic monothymidine repeats in the promoter region of the sole human thymidylate synthetic enzyme is intriguing

Vitamin G: effects of green space on health, well-being, and social safety

BACKGROUND: Looking out on and being in the green elements of the landscape around us seem to affect health, well-being and feelings of social safety. This article discusses the design of a research program on the effects of green space in the living environment on health, well-being and social safety. METHODS/DESIGN: The program consists of three projects at three different scales: at a macro scale using data on the Netherlands as a whole, at an intermediate scale looking into the specific effect of green space in the urban environment, and at micro scale investigating the effects of allotment gardens. The projects are observational studies, combining existing data on land use and health interview survey data, and collecting new data through questionnaires and interviews. Multilevel analysis and GIS techniques will be used to analyze the data. DISCUSSION: Previous (experimental) research in environmental psychology has shown that a natural environment has a positive effect on well-being through restoration of stress and attentional fatigue. Descriptive epidemiological research has shown a positive relationship between the amount of green space in the living environment and physical and mental health and longevity. The program has three aims. First, to document the relationship between the amount and type of green space in people's living environment and their health, well-being, and feelings of safety. Second, to investigate the mechanisms behind this relationship. Mechanisms relate to exposure (leading to stress reduction and attention restoration), healthy behavior and social integration, and selection. Third, to translate the results into policy on the crossroads of spatial planning, public health, and safety. Strong points of our program are: we study several interrelated dependent variables, in different ordinary settings (as opposed to experimental or extreme settings), focusing on different target groups, using appropriate multilevel methods

HCMV Spread and Cell Tropism are Determined by Distinct Virus Populations

Human cytomegalovirus (HCMV) can infect many different cell types in vivo. Two gH/gL complexes are used for entry into cells. gH/gL/pUL(128,130,131A) shows no selectivity for its host cell, whereas formation of a gH/gL/gO complex only restricts the tropism mainly to fibroblasts. Here, we describe that depending on the cell type in which virus replication takes place, virus carrying the gH/gL/pUL(128,130,131A) complex is either released or retained cell-associated. We observed that virus spread in fibroblast cultures was predominantly supernatant-driven, whereas spread in endothelial cell (EC) cultures was predominantly focal. This was due to properties of virus released from fibroblasts and EC. Fibroblasts released virus which could infect both fibroblasts and EC. In contrast, EC released virus which readily infected fibroblasts, but was barely able to infect EC. The EC infection capacities of virus released from fibroblasts or EC correlated with respectively high or low amounts of gH/gL/pUL(128,130,131A) in virus particles. Moreover, we found that focal spread in EC cultures could be attributed to EC-tropic virus tightly associated with EC and not released into the supernatant. Preincubation of fibroblast-derived virus progeny with EC or beads coated with pUL131A-specific antibodies depleted the fraction that could infect EC, and left a fraction that could predominantly infect fibroblasts. These data strongly suggest that HCMV progeny is composed of distinct virus populations. EC specifically retain the EC-tropic population, whereas fibroblasts release EC-tropic and non EC-tropic virus. Our findings offer completely new views on how HCMV spread may be controlled by its host cells