Cross-Presentation of Human Cytomegalovirus pp65 (UL83) to CD8+ T Cells Is Regulated by Virus-Induced, Soluble-Mediator-Dependent Maturation of Dendritic Cells

Cytotoxic CD8+ T lymphocytes (CTL) directed against the matrix protein pp65 are major effectors in controlling infection against human cytomegalovirus (HCMV), a persistent virus of the Betaherpesvirus family. We previously suggested that cross-presentation of pp65 by nonpermissive dendritic cells (DCs) could overcome viral strategies that interfere with activation of CTL (G. Arrode, C. Boccaccio, J. Lule, S. Allart, N. Moinard, J. Abastado, A. Alam, and C. Davrinche, J. Virol. 74:10018-10024, 2000). It is well established that mature DCs are very potent in initiating T-cell-mediated immunity. Consequently, the DC maturation process is a key step targeted by viruses in order to avoid an immune response. Here, we report that immature DCs maintained in coculture with infected human (MRC5) fibroblasts acquired pp65 from early-infected cells for cross-presentation to specific HLA-A2-restricted CTL. In contrast, coculture of DCs in the presence of late-infected cells decreased their capacity to stimulate CTL. Analyses of DC maturation after either coculture with infected MRC5 cells or incubation with infected-cell-conditioned medium revealed that acquisition of a mature phenotype was a prerequisite for efficient stimulation of CTL and that soluble factors secreted by infected cells were responsible for both up and down regulation of CD83 expression on DCs. We identified transforming growth factor beta1 secreted by late HCMV-infected cells as one of these down regulating mediators. These findings suggest that HCMV has devised another means to compromise immune surveillance mechanisms. Together, our data indicate that recognition of HCMV-infected cells by DCs has to occur early after infection to avoid immune evasion and to allow generation of anti-HCMV CTL.     

Web-FACE: a new canopy free-air CO<Subscript>2</Subscript> enrichment system for tall trees in mature forests

The long-term responses of forests to atmospheric CO₂ enrichment have been difficult to determine experimentally given the large scale and complex structure of their canopy. We have developed a CO₂ exposure system that uses the free-air CO₂ enrichment (FACE) approach but was designed for tall canopy trees. The system consists of a CO₂-release system installed within the crown of adult trees using a 45-m tower crane, a CO₂ monitoring system and an automated regulation system. Pure CO₂ gas is released from a network of small tubes woven into the forest canopy (web-FACE), and CO₂ is emitted from small laser-punched holes. The set point CO₂ concentration ([CO₂]) of 500 µmol mol^-1 is controlled by a pulse-width modulation routine that adjusts the rate of CO₂ injection as a function of measured [CO₂] in the canopy. CO₂ consumption for the enrichment of 14 tall canopy trees was about 2 tons per day over the whole growing season. The seasonal daytime mean CO₂ concentration was 520 µmol mol^-1. One-minute averages of CO₂ measurements conducted at canopy height in the center of the CO₂-enriched zone were within ᆨ% and ᆞ% of the target concentration for 76% and 47% of the exposure time, respectively. Despite the size of the canopy and the windy site conditions, performance values correspond to about 75% of that reported for conventional forest FACE with the added advantage of a much simpler and less intrusive infrastructure. Stable carbon isotope signals captured by 80 Bermuda grass (Cynodon dactylon) seedlings distributed within the canopy of treated and control tree districts showed a clearly delineated area, with some nearby individuals having been exposed to a gradient of [CO₂], which is seen as added value. Time-integrated values of [CO₂] derived from the C isotope composition of C. dactylon leaves indicated a mean (-SD) concentration of 513ᇓ µmol mol^-1 in the web-FACE canopy area. In view of the size of the forest and the rough natural canopy, web-FACE is a most promising avenue towards natural forest experiments, which are greatly needed.     

Effects of morphological changes on metal accumulation in a salt marsh sediment of the Skallingen peninsula,Denmark

In 1931 a red-colored, sandy marker horizon was placed on the emergingSkallingen salt marsh. Sedimentation on top of the marker horizon sincethen shows two opposing tendencies. Coincident with salt marshdevelopment the sediments display up to 1964 a fining upward sequencewith an increasing content of organic matter. Since 1964 a nearby creekhas meandered towards the sampling plot. Consequently, the sedimentsbecome coarser with a decreasing organic matter content. Themorphological induced changes in sedimentary conditions strongly influencemetal content in the sediments and thereby hide anthropogenic inducedconcentration variations. Thus, an apparently diminishing Zn content (perkg dry weight) since 1964 could indicate lesser load to the area. However,corrected for grain size effects there is an increasing content of Zn. Othermetal concentrations (e.g. Cu) show a diminishing trend when corrected forgrain size effects and therefore indicate a reduced anthropogenic inducedload of these metals to the salt marsh.     

Following trails of partners in the monogamous lizard, Tiliqua rugosa

The sleepy lizard, Tiliqua rugosa, is an Australian scincid lizard that forms monogamous pairs for 6–8 weeks in the spring before mating occurs. Previous observations and experiments have shown that when partners are separated they can relocate each other, and one suggested mechanism has been trail following. In this article we report results from field-based Y-maze experiments to investigate trail following. In the first part of the spring season, female lizards were more likely to use the arm of the maze previously taken by their male partner than either a blank arm of the maze or the arm taken by an unfamiliar adult male. Females that were more frequently found with their male partner during the spring season were more likely to follow the path of their male partner than less strongly bonded females. In the second part of the spring, after mating had occurred in the natural population, females no longer showed a preference in the maze. Males showed no significant tendency to follow their female partner in any part of the season. The results suggest there is trail following, at least by females, and that females play an active role in maintaining the partnership. This refutes male-based explanations, like mate guarding, for monogamy. Electronic Publication     

Insulin Receptor Substrates Are Essential for the Bioenergetic and Hypertrophic Response of the Heart to Exercise Training

Insulin and insulin-like growth factor 1 (IGF-1) receptor signaling pathways differentially modulate cardiac growth under resting conditions and following exercise training. These effects are mediated by insulin receptor substrate 1 (IRS1) and IRS2, which also differentially regulate resting cardiac mass. To determine the role of IRS isoforms in mediating the hypertrophic and metabolic adaptations of the heart to exercise training, we subjected mice with cardiomyocyte-specific deletion of either IRS1 (CIRS1 knockout [CIRS1KO] mice) or IRS2 (CIRS2KO mice) to swim training. CIRS1KO hearts were reduced in size under basal conditions, whereas CIRS2KO hearts exhibited hypertrophy. Following exercise swim training in CIRS1KO and CIRS2KO hearts, the hypertrophic response was equivalently attenuated, phosphoinositol 3-kinase (PI3K) activation was blunted, and prohypertrophic signaling intermediates, such as Akt and glycogen synthase kinase 3β (GSK3β), were dephosphorylated potentially on the basis of reduced Janus kinase-mediated inhibition of protein phosphatase 2a (PP2A). Exercise training increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) protein content, mitochondrial capacity, fatty acid oxidation, and glycogen synthesis in wild-type (WT) controls but not in IRS1- and IRS2-deficient hearts. PGC-1α protein content remained unchanged in CIRS1KO but decreased in CIRS2KO hearts. These results indicate that although IRS isoforms play divergent roles in the developmental regulation of cardiac size, these isoforms exhibit nonredundant roles in mediating the hypertrophic and metabolic response of the heart to exercise.     

Radiation-induced bystander effects in the Atlantic salmon (salmo salar L.) following mixed exposure to copper and aluminum combined with low-dose gamma radiation

Very little is known about the combined effects of low doses of heavy metals and radiation. However, such “multiple stressor” exposure is the reality in the environment. In the work reported in this paper, fish were exposed to cobalt 60 gamma irradiation with or without copper or aluminum in the water. Doses of radiation ranged from 4 to 75 mGy delivered over 48 or 6 h. Copper doses ranged from 10 to 80 μg/L for the same time period. The aluminum dose was 250 μg/L. Gills and skin were removed from the fish after exposure and explanted in tissue culture flasks for investigation of bystander effects of the exposures using a stress signal reporter assay, which has been demonstrated to be a sensitive indicator of homeostatic perturbations in cells. The results show complex synergistic interactions of radiation and copper. Gills on the whole produce more toxic bystander signals than skin, but the additivity scores show highly variable results which depend on dose and time of exposure. The impacts of low doses of copper and low doses of radiation are greater than additive, medium levels of copper alone have a similar level of effect of bystander signal toxicity to the low dose. The addition of radiation stress, however, produces clear protective effects in the reporters treated with skin-derived medium. Gill-derived medium from the same fish did not show protective effects. Radiation exposure in the presence of 80 μg/L led to highly variable results, which due to animal variation were not significantly different from the effect of copper alone. The results are stressor type, stressor concentration and time dependent. Clearly co-exposure to radiation and heavy metals does not always lead to simple additive effects.     

Ultrasonography survey and thyroid cancer in the Fukushima Prefecture

Thyroid cancer is one of the major health concerns after the accident in the Fukushima Dai-ichi nuclear power station (NPS). Currently, ultrasonography surveys are being performed for persons residing in the Fukushima Prefecture at the time of the accident with an age of up to 18 years. Here, the expected thyroid cancer prevalence in the Fukushima Prefecture is assessed based on an ultrasonography survey of Ukrainians, who were exposed at an age of up to 18 years to ¹³¹I released during the Chernobyl NPS accident, and on differences in equipment and study protocol in the two surveys. Radiation risk of thyroid cancer incidence among survivors of the atomic bombings of Hiroshima and Nagasaki and preliminary estimates of thyroid dose due to the Fukushima accident were used for the prediction of baseline and radiation-related thyroid cancer risks. We estimate a prevalence of thyroid cancer of 0.027 % (95 % CI 0.010 %; 0.050 %) for the first screening campaign in the Fukushima Prefecture. Compared with the incidence rate in Japan in 2007, the ultrasonography survey is predicted to increase baseline thyroid cancer incidence by a factor of 7.4 (95 % CI 0.95; 17.3). Under the condition of continued screening, thyroid cancer during the first fifty years after the accident is predicted to be detected for about 2 % of the screened population. The prediction of radiation-related thyroid cancer in the most exposed fraction (a few ten thousand persons) of the screened population of the Fukushima Prefecture has a large uncertainty with the best estimates of the average risk of 0.1–0.3 %, depending on average dose.     

Can biodiversity hotspots protect more than tropical forest plants and vertebrates?

Conservation International's biodiversity hotspots are areas of high vascular plant endemism combined with high levels of habitat destruction and land use change. Although such hotspots have also been shown to be centres for terrestrial vertebrate endemism, much less is known about how well these areas function as hotspots for other less well‐studied groups, including the hyperdiverse arthropods, other invertebrates and fungi. Because there is a close evolutionary and ecological relationship between insects and plants, we suggest that the potential role of plants as umbrella species for herbivorous insects, potentially herbivorous fungi and nematodes, and parasitic insects should be explored. Finally, we reflect on the increasing social, economic, human conflict and governance issues and the impacts of increasing land use change and global climate change that threaten the biodiversity hotspot system.