Identification of a MHC class-II restricted epitope in carcinoembryonic antigen

Purpose The carcinoembryonic antigen (CEA) is extensively expressed on the vast majority of colorectal, gastric, and pancreatic carcinomas, and, therefore, is a good target for tumor immunotherapy. CD4+ T-helper (Th) cells play a critical role in initiation, regulation, and maintenance of immune responses. In this study, we sought to identify Th epitopes derived from CEA which can induce CEA-specific Th responses. The combined application with cytotoxic T lymphocyte (CTL) epitopes would be more potent than tumor vaccines that primarily activate CTL alone.Methods We utilized a combined approach of using a computer-based algorithm analysis TEPITOPE and in vitro biological analysis to identify Th epitopes in CEA.Results Initial screening of healthy donors showed that all five predicted peptides derived from CEA could induce peptide-specific T-cell proliferation in vitro. We characterized these CEA epitopes by establishing and analyzing peptide-specific T-cell clones. It was shown that CD4+ T-cells specific for the CEA₁₁₆ epitope can recognize and respond to naturally processed CEA protein and CEA₁₁₆ epitope can be promiscuously presented by commonly found major histocompatibility complex (MHC) alleles. Furthermore, it was demonstrated that immunization of human leukocyte antigen (HLA)-DR4 transgenic mice with CEA₁₁₆ peptide elicited antigen-specific Th responses which can recognize the antigenic peptides derived from CEA protein and CEA-positive tumors.Conclusion The MHC class II-restricted epitope CEA₁₁₆ could be used in the design of peptide-based tumor vaccine against several common cancers expressing CEA.     

Inflammation and metabolic dysfunction: links to cardiovascular diseases

Abdominal obesity is a major risk factor for cardiovascular disease, and recent studies highlight a key role of adipose tissue dysfunction, inflammation, and aberrant adipokine release in this process. An increased demand for lipid storage results in both hyperplasia and hypertrophy, finally leading to chronic inflammation, hypoxia, and a phenotypic change of the cellular components of adipose tissue, collectively leading to a substantially altered secretory output of adipose tissue. In this review we have assessed the adipo-vascular axis, and an overview of adipokines associated with cardiovascular disease is provided. This resulted in a first list of more than 30 adipokines. A deeper analysis only considered adipokines that have been reported to impact on inflammation and NF-κB activation in the vasculature. Out of these, the most prominent link to cardiovascular disease was found for leptin, TNF-α, adipocyte fatty acid-binding protein, interleukins, and several novel adipokines such as lipocalin-2 and pigment epithelium-derived factor. Future work will need to address the potential role of these molecules as biomarkers and/or drug targets.     

Integrative freshwater ecology and biodiversity conservation

Freshwater ecosystems provide goods and services of critical importance to human societies, yet they are among the most heavily altered ecosystems with an overproportional loss of biodiversity. Major threats to freshwater biodiversity include overexploitation, water pollution, fragmentation, destruction or degradation of habitat, and invasions by non-native species. Alterations of natural flow regimes by man-made dams, land-use changes, river impoundments, and water abstraction often have profound impacts on lotic communities. An understanding of the functional interactions and processes in freshwater ecosystems presents a major challenge for scientists, but is crucial for effective and sustainable restoration. Most conservation approaches to date have considered single species or single level strategies. In contrast, the concept of ‘Integrative Freshwater Ecology and Biodiversity Conservation’ (IFEBC) proposed herein addresses the interactions between abiotic and biotic factors on different levels of organization qualitatively and quantitatively. It consequently results in a more holistic understanding of biodiversity functioning and management. Core questions include modeling of the processes in aquatic key habitats and their functionality based on the identification and quantification of factors which control the spatial and temporal distribution of biodiversity and productivity in aquatic ecosystems. The context and importance of research into IFEBC is illustrated using case studies from three major areas of research: (i) aquatic habitat quality and restoration ecology, (ii) the genetic and evolutionary potential of aquatic species, and (iii) the detection of stress and toxic effects in aquatic ecosystems using biomarkers. In conclusion, our understanding of the functioning of aquatic ecosystems and conservation management can greatly benefit from the methodological combination of molecular and ecological tools.     

Coordinated Control of mRNA and rRNA Processing Controls Embryonic Stem Cell Pluripotency and Differentiation

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Defaunation impacts on seed survival and its effect on the biomass of future tropical forests

Large animal species, which provide important ecological functions such as dispersal of seeds or top–down control of seed predators, are very vulnerable in fragmented forests, being unable to survive in small fragments, and facing increasing hunting pressure. The loss of large animals affects two main ecological processes crucial for the tree reproductive cycle: seed dispersal of large seeds (e.g. provided by tapirs) and control of seed predator population (e.g. provided by large cats). The changes in both processes are expected to increase seed mortality since seeds are not dispersed away from conspecifics (causing increased pre‐dispersal mortality due to negative density dependent effects) and/or face increased predation after a dispersal event (post‐dispersal mortality). Although an extensive body of empirical knowledge exists on seed predation, the link between seed loss and adult tree community composition and structure is not well established, as well as the temporal scale seed changes affect adults. Using an individual‐based forest model (FORMIND), we evaluate the long‐term consequences of increased pre and post‐dispersal seed mortality on the future forest biomass retention of a Brazilian northeastern Atlantic forest. Our results show that forest biomass is significantly affected after 80–93% pre‐dispersal loss of large seeds, or post‐dispersal predation densities of 20–25 predators per parent tree. Large‐seeded tree species are at increased risk of local extinction causing up to 26.2% loss of forest biomass when both pre and post‐dispersal processes are combined. However, these changes can last up to 100 years after the occurrence of defaunation. In summary we conclude that large animal loss has the potential to reduce future forest biomass and tree species‐richness by impacting seed survival, and should be considered in the planning of biodiversity friendly landscapes as well as in calculations of the global carbon budget.     

Increased Soil Frost Versus Summer Drought as Drivers of Plant Biomass Responses to Reduced Precipitation: Results from a Globally Coordinated Field Experiment

Reduced precipitation treatments often are used in field experiments to explore the effects of drought on plant productivity and species composition. However, in seasonally snow-covered regions reduced precipitation also reduces snow cover, which can increase soil frost depth, decrease minimum soil temperatures and increase soil freeze–thaw cycles. Therefore, in addition to the effects of reduced precipitation on plants via drought, freezing damage to overwintering plant tissues at or below the soil surface could further affect plant productivity and relative species abundances during the growing season. We examined the effects of both reduced rainfall (via rain-out shelters) and reduced snow cover (via snow removal) at 13 sites globally (primarily grasslands) within the framework of the International Drought Experiment, a coordinated distributed experiment. Plant cover was estimated at the species level, and aboveground biomass was quantified at the functional group level. Among sites, we observed a negative correlation between the snow removal effect on minimum soil temperature and plant biomass production the next growing season. Three sites exhibited significant rain-out shelter effects on plant productivity, but there was no correlation among sites between the rain-out shelter effect on minimum soil moisture and plant biomass. There was no interaction between snow removal and rain-out shelters for plant biomass, although these two factors only exhibited significant effects simultaneously for a single site. Overall, our results reveal that reduced snowfall, when it decreases minimum soil temperatures, can be an important component of the total effect of reduced precipitation on plant productivity.     

Fe(III) as an electron acceptor for H2 oxidation in thermophilic anaerobic enrichment cultures from geothermal areas

Six sustainable enrichment cultures of thermophilic H₂-oxidizing microorganisms utilizing Fe(III) as an electron acceptor were obtained from geothermally heated environments located on two continents (America, Eurasia) and on islands in the Northern (Iceland) and Southern (Fiji) hemispheres, demonstrating the wide distribution of these microorganisms. The main products of amorphic Fe(III) oxide reduction were magnetite and siderite. The observed temperature range for Fe(III) reduction in growing cultures was from 55°C to 87°C, extending the known limits for growth of Fe(III)-reducing microorganisms producing extracellular magnetite to nearly 90°C. Received: August 13, 1996 / Accepted: January 17, 1997