thermo-msf-parser: An Open Source Java Library to Parse and Visualize Thermo Proteome Discoverer msf Files

The Thermo Proteome Discoverer program integrates both peptide identification and quantification into a single workflow for peptide-centric proteomics. Furthermore, its close integration with Thermo mass spectrometers has made it increasingly popular in the field. Here, we present a Java library to parse the msf files that constitute the output of Proteome Discoverer. The parser is also implemented as a graphical user interface allowing convenient access to the information found in the msf files, and in Rover, a program to analyze and validate quantitative proteomics information. All code, binaries, and documentation is freely available at http://thermo-msf-parser.googlecode.com.acceptedVersio

Suppression of natural killer cell activity in harbour seals (Phoca vitulina) fed Baltic Sea herring

Mass mortalities among marine mammal populations in recent years have raised questions about a possible contributory role of contaminants accumulated through the marine food chain. While viruses were shown to be the primary cause of the outbreaks, an immunotoxic action by organochlorine chemicals in affected animals could not be ruled out. We carried out a 2 1/2 -year immunotoxicological experiment in which two groups of 11 harbour seals each were fed herring from either the relatively contaminated Baltic Sea or the relatively uncontaminated Atlantic Ocean. Seals in the Baltic Sea group accumulated 3-4 times higher levels of Ah-receptor-mediated 2,3,7,8-TCDD Toxic Equivalents in blubber than did their Atlantic counterparts following 2 years on the respective diets. Blood was sampled a total of 17 times during the course of the experiment for immunological evaluation, during which time the natural cytotoxic activity of peripheral blood mononuclear cells isolated from seals fed Baltic Sea herring declined to a level approximately 2

Impairment of Immune Function in Harbor Seals (Phoca vitulina) Feeding on Fish from Polluted Waters

Disease outbreaks with high mortality rates among seals and dolphins have recently attracted considerable public and scientific interest. Allhouyh in most cases morbillivirus infections were shown to be the primary cause of the disease outbreaks, it was speculated that pollution-induced immunosuppression had playat:! a contributory role. Here we present results of a prospective study under semifield conditions, in which two groups of harbor seals (Phoca vitulina) were fed herring from marine regions with different contamination levels; the hig

Host resistance to rat cytomegalovirus (RCMV) and immune function in adult PVG rats fed herring from the contaminated Baltic Sea

The immunotoxic potential of many classes of environmental contaminants has been well established in laboratory studies, with much attention being focussed on aryl hydrocarbon (Ah)-receptor binding polychlorinated biphenyl (PCB), polychlorinated dibenzo-p-dioxin (PCDD), and polychlorinated dibenzofuran (PCDF) congeners. In a semi-field study, we previously showed that harbour seals (Phoca vitulina) fed herring from the contaminated Baltic Sea had lower natural killer cell activity, T-lymphocyte functionality and delayed-type hypersensitivity responses than seals fed herring from the relatively uncontaminated Atlantic Ocean. While ethical and practical constraints preclude in-depth studies in seals, specific reagents and a wider array of immune function tests allow such studies in laboratory rats. We therefore carried out a feeding study in rats aimed at extending our observations of contaminant-induced immunosuppression in harbour seals. The same two herring batches used in the seal study were freeze-dried, supplemented and fed. to female adult PVG rats for a period of 4 1/4 months. Daily contaminant intakes of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalents (TEQ) were estimated to be 0.3 ng/kg body weight and 1.6 ng/kg in the Atlantic and Baltic groups, respectively. At the end of the feeding experiment, no contaminant-related changes in spleen CD4+/CD8+cellularity, natural killer cell activity, or mitogen-induced proliferative responses of thymus or spleen cells could be detected. However, total thymocyte numbers and thymus CD4+/CD8+ratios were reduced in the Baltic group. A novel model was established to assess the specific T-cell response to rat cytomegalovirus (RCMV). When applied to the feeding study, no differences between the Atlantic and Baltic groups in the RCMV-induced proliferative T-lymphocyte responses could be detected, but virus titres in salivary glands of infected rats of the Baltic Sea group were higher. These elevated RCMV titres and changes in thymus cellularity suggest that the dietary exposure to low levels of contaminants may have been immunotoxic at a level which our immune function test could not otherwise detect. While the herring diet per se appeared to have an effect on several immune function parameters, lower plasma thyroid hormone levels in the Baltic Sea group of rats confirmed that exposure to the environmental mixture of contaminants led to adverse PHAH-related health effects

Short term fasting does not aggravate immunosuppression in harbour seals (Phoca vitulina) with high body burdens of organochlorines

Two groups of 11 harbour seals (Phoca vitulina) with different body burdens of organochlorines were subjected to an experimental 15-day fasting period, during which they lost an average 16.5% of their body weights. Blood levels of the most persistent organochlorines showed an approximate twofold increase, while levels of aryl hydrocarbon receptor-binding organochlorines remained largely unaffected. Few differences in immunological parameters were observed between the two dietary groups. Numbers of circulating lymphocytes dropped to about 65% of the initial values and NK cell activity showed a slight increase in both groups. Mitogen- and antigen-induced lymphoproliferative responses of the Baltic group of seals remained within normal ranges. These results suggest that relatively short-term fasting periods do not present an additional immunotoxicological risk to seals with high body burdens of organochlorines

Increased aggression during pregnancy comes at a higher metabolic cost

Aggressive behaviour is linked to fitness, but it is metabolically costly. Changes in metabolic demand during the reproductive cycle could constrain activity and thereby modulate behavioural phenotypes. We predicted that increased metabolic demands in late pregnancy would lead to reduced aggression and a lower metabolic cost of behaviour in the mosquitofish Gambusia holbrooki. Contrary to our prediction, females became more aggressive in late pregnancy, but metabolic scope (i.e. the metabolic energy available for activity and behaviour) decreased. Consequently, late-stage pregnant females spent significantly more of their available metabolic scope on aggressive behaviour. Hence, as pregnancy progressed, females showed increasingly risky behaviour by depleting metabolic resources available for activities other than fighting. We argue that the metabolic cost of behaviour, and possibly personality, is best expressed with reference to metabolic scope, rather than resting metabolic rates or concentrations of metabolites. This dependence on metabolic scope could render reproductive success sensitive to environmental changes

Cross-priming of cyclin B1, MUC-1 and survivin-specific CD8(+ )T cells by dendritic cells loaded with killed allogeneic breast cancer cells

INTRODUCTION: The ability of dendritic cells (DCs) to take up whole tumor cells and process their antigens for presentation to T cells ('cross-priming') is an important mechanism for induction of tumor specific immunity. METHODS: In vitro generated DCs were loaded with killed allogeneic breast cancer cells and offered to autologous naïve CD8(+ )T cells in 2-week and/or 3-week cultures. CD8(+ )T cell differentiation was measured by their capacity to secrete effector cytokines (interferon-γ) and kill breast cancer cells. Specificity was measured using peptides derived from defined breast cancer antigens. RESULTS: We found that DCs loaded with killed breast cancer cells can prime naïve CD8(+ )T cells to differentiate into effector cytotoxic T lymphocytes (CTLs). Importantly, these CTLs primed by DCs loaded with killed HLA-A*0201(- )breast cancer cells can kill HLA-A*0201(+ )breast cancer cells. Among the tumor specific CTLs, we found that CTLs specific for HLA-A2 restricted peptides derived from three well known shared breast tumor antigens, namely cyclin B1, MUC-1 and survivin. CONCLUSION: This ability of DCs loaded with killed allogeneic breast cancer cells to elicit multiantigen specific immunity supports their use as vaccines in patients with breast cancer

Cross-Priming of Naive Cd8 T Cells against Melanoma Antigens Using Dendritic Cells Loaded with Killed Allogeneic Melanoma Cells

The goal of tumor immunotherapy is to elicit immune responses against autologous tumors. It would be highly desirable that such responses include multiple T cell clones against multiple tumor antigens. This could be obtained using the antigen presenting capacity of dendritic cells (DCs) and cross-priming. That is, one could load the DC with tumor lines of any human histocompatibility leukocyte antigen (HLA) type to elicit T cell responses against the autologous tumor. In this study, we show that human DCs derived from monocytes and loaded with killed melanoma cells prime naive CD45RA+CD27+CD8+ T cells against the four shared melanoma antigens: MAGE-3, gp100, tyrosinase, and MART-1. HLA-A201+ naive T cells primed by DCs loaded with HLA-A201− melanoma cells are able to kill several HLA-A201+ melanoma targets. Cytotoxic T lymphocyte priming towards melanoma antigens is also obtained with cells from metastatic melanoma patients. This demonstration of cross-priming against shared tumor antigens builds the basis for using allogeneic tumor cell lines to deliver tumor antigens to DCs for vaccination protocols