The 7R polymorphism in the dopamine receptor D4 gene (DRD4) is associated with financial risk taking in men

Individuals exhibit substantial heterogeneity in financial risk aversion. Recent work on twins demonstrated that some variation is influenced by individual heritable differences. Despite this, there has been no study investigating possible genetic loci associated with financial risk taking in healthy individuals. Here, we examined whether there is an association between financial risk preferences, elicited experimentally in a game with real monetary payoffs, and the presence of the 7-repeat allele (7R+) in the dopamine receptor D₄ gene as well as the presence of the A1 allele (A1+) in the dopamine receptor D₂ gene in 94 young men. Although we found no association between the A1 allele and risk preferences, we did find that 7R+ men are significantly more risk loving than 7R? men. This polymorphism accounts for roughly 20% of the heritable variation in financial risk taking. We suggest that selection for the 7R allele may be for a behavioral phenotype associated with risk taking. This is consistent with previous evolutionary explanations suggesting that selection for this allele was for behaviors associated with migration and male competition, both of which entail an element of risk.     

Side-effects of organic and synthetic pesticides on cold-stored diapausing prepupae of <Emphasis Type="Italic">Trichogramma cordubensis</Emphasis>

The side-effects of three insecticides (deltamethrin, lambda-cyhalothrin and Bacillus thuringiensis Berliner) and one fungicide (basic copper sulphate) were tested on cold-stored diapausing prepupae of Trichogramma cordubensis Vargas and Cabello (Hymenoptera: Trichogrammatidae). Pesticides were directly sprayed on parasitized host eggs (being the diapausing parasitoids in the prepupal stage) after cold storage (3°C) for three different periods (60, 120 and 180 days). Regardless of the period of cold storage, both pyrethroids reduced the emergence rates of T. cordubensis (both <25%) compared to the control (emergence varied from 83% to 89%). The most toxic pyrethroid was lambda-cyhalothrin; Trichogramma cordubensis adult emergence varied from 7% to 15%. Lambda-cyhalothrin also negatively affected the longevity and fecundity of parasitoids cold stored for 60 days. Bacillus thuringiensis Berliner subsp. kurstaki and basic copper sulphate had little or no adverse effect on emergence rates (generally >80%), longevity nor fecundity of T. cordubensis, indicating that these pesticides could be successfully integrated into pest management programs using wasps that were cold stored under diapause. Such integration would be valuable to pest management programs by reducing the costs of T. cordubensis mass rearing and by allowing producers to stockpile parasitoids for release in the growing season. However, since the emergence rate, longevity and fecundity of T. cordubensis generally decreased with increasing duration in cold storage, wasps to be used in integrated pest management programs should only be stored at 3°C for 60 days maximum. Handling Editor: Sam Cook.     

The Not-so-Dark Ages: ecology for human growth in medieval and early twentieth century Portugal as inferred from skeletal growth profiles

This study attempts to address the issue of relative living standards in Portuguese medieval and early 20th century periods. Since the growth of children provides a good measure of environmental quality for the overall population, the skeletal growth profiles of medieval Leiria and early 20th century Lisbon were compared. Results show that growth in femur length of medieval children did not differ significantly from that of early 20th century children, but after puberty medieval adolescents seem to have recovered, as they have significantly longer femora as adults. This is suggestive of greater potential for catch-up growth in medieval adolescents. We suggest that this results from distinct child labor practices, which impact differentially on the growth of Leiria and Lisbon adolescents. Work for medieval children and adolescents were related to family activities, and care and attention were provided by family members. Conversely, in early 20th century Lisbon children were more often sent to factories at around 12 years of age as an extra source of family income, where they were exploited for their labor. Since medieval and early 20th century children were stunted at an early age, greater potential for catch-up growth in medieval adolescents results from exhausting work being added to modern adolescent's burdens of disease and poor diet, when they entered the labor market. Although early 20th century Lisbon did not differ in overall unfavorable living conditions from medieval Leiria, after puberty different child labor practices may have placed modern adolescents at greater risk of undernutrition and poor growth.     

Physalin B inhibits Rhodnius prolixus hemocyte phagocytosis and microaggregation by the activation of endogenous PAF-acetyl hydrolase activities

The effects of physalin B (a natural secosteroidal chemical from Physalis angulata, Solanaceae) on phagocytosis and microaggregation by hemocytes of 5th-instar larvae of Rhodnius prolixus were investigated. In this insect, hemocyte phagocytosis and microaggregation are known to be induced by the platelet-activating factor (PAF) or arachidonic acid (AA) and regulated by phospholipase A₂ (PLA₂) and PAF-acetyl hydrolase (PAF-AH) activities. Phagocytic activity and formation of hemocyte microaggregates by Rhodnius hemocytes were strongly blocked by oral treatment of this insect with physalin B (1 μg/mL of blood meal). The inhibition induced by physalin B was reversed for both phagocytosis and microaggregation by exogenous arachidonic acid (10 μg/insect) or PAF (1 μg/insect) applied by hemocelic injection. Following treatment with physalin B there were no significant alterations in PLA₂ activities, but a significant enhancement of PAF-AH was observed. These results show that physalin B inhibits hemocytic activity by depressing insect PAF analogous (iPAF) levels in hemolymph and confirm the role of PAF-AH in the cellular immune reactions in R. prolixus.     

Arachidonic Acid Stimulates Cell Adhesion through a Novel p38 MAPK-RhoA Signaling Pathway That Involves Heat Shock Protein 27

Rho GTPases are critical components of cellular signal transduction pathways. Both hyperactivity and overexpression of these proteins have been observed in human cancers and have been implicated as important factors in metastasis. We previously showed that dietary n-6 fatty acids increase cancer cell adhesion to extracellular matrix proteins, such as type IV collagen. Here we report that in MDA-MB-435 human melanoma cells, arachidonic acid activates RhoA, and inhibition of RhoA signaling with either C3 exoenzyme or dominant negative Rho blocked arachidonic acid-induced cell adhesion. Inhibition of the Rho kinase (ROCK) with either small molecule inhibitors or ROCK II-specific small interfering RNA (siRNA) blocked the fatty acid-induced adhesion. However, unlike other systems, inhibition of ROCK did not block the activation of p38 mitogen-activated protein kinase (MAPK); instead, Rho activation depended on p38 MAPK activity and the presence of heat shock protein 27 (HSP27), which is phosphorylated downstream of p38 after arachidonic acid treatment. HSP27 associated with p115RhoGEF in fatty acid-treated cells, and this association was blocked when p38 was inhibited. Furthermore, siRNA knockdown of HSP27 blocked the fatty acid-stimulated Rho activity. Expression of dominant negative p115-RhoGEF or p115RhoGEF-specific siRNA inhibited both RhoA activation and adhesion on type IV collagen, whereas a constitutively active p115RhoGEF restored the arachidonic acid stimulation in cells in which the p38 MAPK had been inhibited. These data suggest that n-6 dietary fatty acids stimulate a set of interactions that regulates cell adhesion through RhoA and ROCK II via a p38 MAPK-dependent association of HSP27 and p115RhoGEF.The ability of tumor cells to metastasize to secondary sites is a hallmark of neoplastic disease. Unfortunately, this propensity to spread is the primary cause of morbidity and death in cancer patients (1). Metastasis is clearly a highly regulated, multistep process that occurs in a spatiotemporal manner (2–4). To escape the restrictive compartment boundaries characteristic of adult tissue, separate intravasation and extravasation steps requiring alterations in co-adhesion, adhesion, invasion, and migration must occur. Execution of these biological processes, involving multiple proteins and cellular organelles, require highly coordinated cell signaling mechanisms.The Rho family of small GTPases regulates many facets of cytoskeletal rearrangements that facilitate cell attachment and migration (5–7). Rho GTPases act as molecular switches by changing from an inactive GDP-bound conformation to an active GTP-bound conformation, thereby regulating a signaling pathway. These proteins are directly regulated by Rho guanine nucleotide exchange factors (GEFs),² Rho GTPase activating proteins, and Rho GDP-dissociation inhibitors (8–12). RhoGEFs bind to the GTPase to catalyze the dissociation of GDP, allowing the binding of GTP and thereby promoting Rho activation (8). The RGS (regulators of G protein signaling) domain-containing RhoGEFs are a recently described family of GEFs. Currently, there are three members of this family, PDZ-RhoGEF, LARG, and p115RhoGEF (13–15), in which the RGS domains function as a heterotrimeric GTPase-activating domain (13, 15, 16). The RGS family of RhoGEFs has been shown to regulate Rho during several processes including cytoskeletal rearrangements, cell adhesion, and cancer progression (17–21).There is significant interplay between the activity of small GTPases and signaling derived from fatty acid metabolism (22–28). Linoleic acid, which is metabolized to arachidonic acid, is an n-6 polyunsaturated fatty acid that is present at high levels in most western diets (29). In animal models, diets high in n-6 polyunsaturated fatty acids have been shown to enhance tumor progression and metastasis (30, 31). Additionally, arachidonic acid is stored in cell membranes and is made available by phospholipases under conditions of increased inflammatory response (32). Arachidonic acid is further metabolized by cyclooxygenases (COX), lipoxygenases (LOX), and cytochrome P450 monooxygenases to yield bioactive products that have myriad effects on cells, and altered metabolism of arachidonic acid by COX, LOX, and P450 has been implicated in cancer progression (31, 33–36).We have studied mechanisms of cell adhesion using the MDA-MB-435 cells as a model of a highly metastatic human cancer cell line (37). These cells have been extensively studied for their ability to recapitulate the metastatic cascade in vivo and in vitro, although recent work indicates that the cells currently in use are most likely a human melanoma line (38). We initially observed that arachidonic acid (AA) enhanced adhesion of MDA-MB-435 cells to type IV collagen through specific integrin-mediated pathways (37). Exogenous AA led to the activation of mitogen-activated protein kinase (MAPK)-activated protein kinase 2 and the phosphorylation of heat shock protein 27 (HSP27) via a p38 MAPK-dependent process (39). Inhibition of p38 MAPK activation blocked cell adhesion as did function-blocking antibodies specific for subunits of the collagen receptor (40). More recently, we identified the key metabolite of AA (15-(S)- hydroxyeicosatetraenoic acid) and the upstream kinases (TAK1 and MKK6) that are responsible for activation of p38 MAPK in this system (41).In this study we investigated the role of Rho activation in the MDA-MB-435 cells after exposure to arachidonic acid. Several aspects of the regulation of Rho signaling in these cells provide insights into the cross-talk between important signaling pathways.     

Impacts of increased sediment loads on the ecology of lakes

Increased sediment loading comprises one of the most important and pervasive anthropogenic impacts on aquatic ecosystems globally. In spite of this, little is known of the overall effects of increased sediment loads on lakes. By modifying both bottom-up and top-down ecological processes and restructuring energy flow pathways, increased sediment loads not only alter biotic assemblage structure and ecological functioning significantly, but frequently result in reduced biological diversity and productivity. Although lake food-webs can be subsidised to some extent by the adsorption of organic carbon to fine sediments, trophic structure and the composition of biotic assemblages remain likely to be modified considerably. The mineralogy and particle size of sediments and the availability of nutrients, by influencing both the scale and nature of impacts, are key determinants of the overall effects of increased sediment loads on lake ecosystems. Although interactions with other global anthropogenic pressures, such as invasion by exotic species and climate change, are likely to be significant, little remains known about the nature or likely strength of those interactions. Widespread increases in sediment loading to lakes have, therefore, profound implications for the conservation and management of global aquatic biological diversity.     

Using multiplexed regulation of luciferase activity and GFP translocation to screen for FOXO modulators

Background  

Independent luciferase reporter assays and fluorescent translocation assays have been successfully used in drug discovery for several molecular targets. We developed U2transLUC, an assay system in which luciferase and fluorescent read-outs can be multiplexed to provide a powerful cell-based high content screening method.