Robust T cell responses to aspergillosis in chronic granulomatous disease: implications for immunotherapy.

Chronic granulomatous disease (CGD) patients are highly susceptible to invasive aspergillosis and might benefit from aspergillus-specific T cell immunotherapy, which has shown promise in treating those with known T cell defects such as haematopoietic stem cell transplant (HSCT) recipients. But whether such T cell defects contribute to increased risks for aspergillus infection in CGD is unclear. Hence, we set out to characterize the aspergillus-specific T cell response in CGD. In murine CGD models and in patients with CGD we showed that the CD4(+) T cell responses to aspergillus were unimpaired: aspergillus-specific T cell frequencies were even elevated in CGD mice (P < 0·01) and humans (P = 0·02), compared to their healthy counterparts. CD4-depleted murine models suggested that the role of T cells might be redundant because resistance to aspergillus infection was conserved in CD4(+) T cell-depleted mice, similar to wild-type animals. In contrast, mice depleted of neutrophils alone or neutrophils and CD4(+) T cells developed clinical and pathological evidence of pulmonary aspergillosis and increased mortality (P < 0·05 compared to non-depleted animals). Our findings that T cells in CGD have a robust aspergillus CD4(+) T cell response suggest that CD4(+) T cell-based immunotherapy for this disease is unlikely to be beneficial.

Top-down control of soil fungal community composition by a globally distributed keystone consumer.

The relative contribution of top-down and bottom-up processes regulating primary decomposers can influence the strength of the link between the soil animal community and ecosystem functioning. Although soil bacterial communities are regulated by bottom-up and top-down processes, the latter are considered to be less important in structuring the diversity and functioning of fungal-dominated ecosystems. Despite the huge diversity of mycophagous (fungal-feeding) soil fauna, and their potential to reverse the outcomes of competitive fungal interactions, top-down grazing effects have never been found to translate to community-level changes. We constructed soil mesocosms to investigate the potential of isopods grazing on cord-forming basidiomycete fungi to influence the community composition and functioning of a complex woodland soil microbial community. Using metagenomic sequencing we provide conclusive evidence of direct top-down control at the community scale in fungal-dominated woodland soil. By suppressing the dominant cord-forming basidiomycete fungi, isopods prevented the competitive exclusion of surrounding litter fungi, increasing diversity in a community containing several hundred fungal species. This isopod-induced modification of community composition drove a shift in the soil enzyme profile, and led to a restructuring of the wider mycophagous invertebrate community. We highlight characteristics of different soil ecosystems that will give rise to such top-down control. Given the ubiquity of isopods and basidiomycete fungi in temperate and boreal woodland ecosystems, such top-down community control could be of widespread significance for global carbon and nutrient cycling.

Bottom-up determination of soil collembola diversity and population dynamics in response to interactive climatic factors.

Soil invertebrate contributions to decomposition are climate dependent. Understanding the influence of abiotic factors on soil invertebrate population dynamics will strengthen predictions regarding ecosystem functioning under climate change. As well as being important secondary decomposers, mycophagous collembola exert a strong influence on the growth and activity of primary decomposers, particularly fungi. Species-specific grazing preferences for different fungi enable fungal community composition to influence the direct impacts of climate change on collembola populations. We investigate the interactive roles of altered abiotic conditions (warming, wetting and drying) and the identity of the dominant decomposer fungus in determining collembola community dynamics in woodland soil mesocosms. The bottom-up influence of the dominant component of the fungal resource base was an important mediator of the direct climatic impacts on collembola populations. The positive influences of warming and wetting, and the negative influence of drying, on collembola abundance and diversity were much less pronounced in fungal-inoculation treatments, in which populations were reduced compared with uninoculated mesocosms. We conclude that the thick, sclerotised cords of the competitively dominant decomposer fungi reduced the biomass of smaller, more palatable soil fungi, limiting the size of collembola populations and their ability to respond to altered abiotic conditions.

Transplantation of human renal carcinomas into athymic mice.

Thirty-one primary human renal carcinomas were transplanted into athymic mice of which ten produced tumors in the mouse host. Only tumors with a nuclear grade of 3 or 4 were successfully transplanted. The nuclear grades of the human tumor and transplant were similar; however, the cellular histology often varied. Patient prognosis appeared to be inversely related to successful tumor transplantation. In the transplant group, the 1-year survival was 30% in contrast to a 1-year survival of 83% among patients with renal cancers of similar stage and grade which did not produce tumors in the mice.

Characterization of two human cell lines (TK-10, TK-164) of renal cell cancer.

Two previously unreported cell lines of human renal cell carcinoma are presented. TK-10 and TK-164 have each been in culture for over 4 years. The epithelial nature of both cell lines has been documented by light and electron microscopy. The cells in each line contain a Y chromosome, have specific marker chromosomes, and a distinct flow cytometric histogram. Both lines grow in agar, albeit not in athymic mice.

A simple appliance to correct mandibular deviation following hemimandibulectomy.

An appliance is described for the rehabilitation of patients following hemimandibulectomy. It has the advantages, over traditional prostheses, of being quick, simple and cheap to produce.

Effects of elevated CO2 on litter chemistry and subsequent invertebrate detritivore feeding responses.

Elevated atmospheric CO2 can change foliar tissue chemistry. This alters leaf litter palatability to macroinvertebrate detritivores with consequences for decomposition, nutrient turnover, and food-web structure. Currently there is no consensus on the link between CO2 enrichment, litter chemistry, and macroinvertebrate-mediated leaf decomposition. To identify any unifying mechanisms, we presented eight invertebrate species from aquatic and terrestrial ecosystems with litter from Alnus glutinosa (common alder) or Betula pendula (silver birch) trees propagated under ambient (380 ppm) or elevated (ambient +200 ppm) CO2 concentrations. Alder litter was largely unaffected by CO2 enrichment, but birch litter from leaves grown under elevated CO2 had reduced nitrogen concentrations and greater C/N ratios. Invertebrates were provided individually with either (i) two litter discs, one of each CO2 treatment ('choice'), or (ii) one litter disc of each CO2 treatment alone ('no-choice'). Consumption was recorded. Only Odontocerum albicorne showed a feeding preference in the choice test, consuming more ambient- than elevated-CO2 birch litter. Species' responses to alder were highly idiosyncratic in the no-choice test: Gammarus pulex and O. albicorne consumed more elevated-CO2 than ambient-CO2 litter, indicating compensatory feeding, while Oniscus asellus consumed more of the ambient-CO2 litter. No species responded to CO2 treatment when fed birch litter. Overall, these results show how elevated atmospheric CO2 can alter litter chemistry, affecting invertebrate feeding behaviour in species-specific ways. The data highlight the need for greater species-level information when predicting changes to detrital processing-a key ecosystem function-under atmospheric change.

Contrasting effects of elevated temperature and invertebrate grazing regulate multispecies interactions between decomposer fungi.

Predicting the influence of biotic and abiotic factors on species interactions and ecosystem processes is among the primary aims of community ecologists. The composition of saprotrophic fungal communities is a consequence of competitive mycelial interactions, and a major determinant of woodland decomposition and nutrient cycling rates. Elevation of atmospheric temperature is predicted to drive changes in fungal community development. Top-down regulation of mycelial growth is an important determinant of, and moderator of temperature-driven changes to, two-species interaction outcomes. This study explores the interactive effects of a 4 °C temperature increase and soil invertebrate (collembola or woodlice) grazing on multispecies interactions between cord-forming basidiomycete fungi emerging from colonised beech (Fagus sylvatica) wood blocks. The fungal dominance hierarchy at ambient temperature (16 °C; Phanerochaete velutina > Resinicium bicolor > Hypholoma fasciculare) was altered by elevated temperature (20 °C; R. bicolor > P. velutina > H. fasciculare) in ungrazed systems. Warming promoted the competitive ability of the fungal species (R. bicolor) that was preferentially grazed by all invertebrate species. As a consequence, grazing prevented the effect of temperature on fungal community development and maintained a multispecies assemblage. Decomposition of fungal-colonised wood was stimulated by warming, with implications for increased CO2 efflux from woodland soil. Analogous to aboveground plant communities, increasing complexity of biotic and abiotic interactions appears to be important in buffering climate change effects on soil decomposers.

Supporting new vaccine introduction decisions: lessons learned from the Hib Initiative experience.

The introduction of Haemophilus influenzae type b (Hib) vaccine in developing countries has suffered from a long delay. Between 2005 and 2009, a surge in Hib vaccine adoption took place, particularly among GAVI-eligible countries. Several factors contributed to the increase in Hib vaccine adoption, including support provided by the Hib Initiative, a project funded by the GAVI Alliance in 2005 to accelerate evidence-informed decisions for use of Hib vaccine. This paper reviews the strategy adopted by the Hib Initiative and the lessons learned in the process, which provide a useful model to accelerate uptake of other new vaccines.

The predatory response of a stalking spider, Plexippus paykulli, to camouflage and prey type

When approaching prey, a stalking predator should consider trade-offs between the probabilities of early detection (by the prey, before the strike), spontaneous departure (of prey, before the strike), prey escape (following the strike) and interference (by rivals or predators). In this study we tested the response of a jumping spider, Plexippus paykullito a background with two different camouflaging properties, and two different prey types (maggots versus adult house flies). Spiders jumped towards adult house flies from greater distances on a non-camouflaging background, but background colour had no effect on jumping distance when the prey were maggots. Spiders stalking both prey types approached more slowly when camouflaged. Our experiments suggest that jumping spiders may be responding to changes in the trade-off relationships between the probabilities of early detection, spontaneous departure, escape and interference.Copyright 1997 The Association for the Study of Animal Behaviour1997The Association for the Study of Animal Behaviour

Abnormal cholesterol metabolism in renal clear cell carcinoma.

The clear cell form of renal cell carcinoma is known to derive its histologic appearance from accumulations of glycogen and lipid. We have found that the most consistently stored lipid form is cholesteryl ester. Clear cell cancer tissue contained 8-fold more total cholesterol and 35-fold more esterified cholesterol than found in normal kidney. Cholesteryl ester appeared to be formed intracellularly since it was not membrane-bound and since oleate was the predominant form, as opposed to linoleate in lipoprotein cholesteryl esters. The cholesterol in clear cell tumors did not appear to be a result of excessive synthesis from acetate since HMG-CoA reductase (EC 1.1.1.34) activity was lower in cancer tissue than in normal kidney (2.9 +/- 0.8 vs. 7.2 +/- 1.2 pmol/mg of protein per min). In contrast, intracellular activity of fatty acyl-coenzyme A:cholesterol acyl transferase (ACAT, EC 2.3.1.26) was higher in tumor tissue than in normal kidney (2405 +/- 546 vs. 1326 +/- 301 pmol/mg of protein per 20 min) while cytosolic cholesteryl ester hydrolase activity appeared normal. Cholesteryl ester storage in clear cell renal cancer may be a result of a primary abnormality in ACAT activity or it may be a result of reduced release of free cholesterol (relative to cell content) with a secondary elevation in ACAT activity.