Modelling a Particle Detector in Field Theory

Particle detector models allow to give an operational definition to the particle content of a given quantum state of a field theory. The commonly adopted Unruh-DeWitt type of detector is known to undergo temporary transitions to excited states even when at rest and in the Minkowski vacuum. We argue that real detectors do not feature this property, as the configuration "detector in its ground state + vacuum of the field" is generally a stable bound state of the underlying fundamental theory (e.g. the ground state-hydrogen atom in a suitable QED with electrons and protons) in the non-accelerated case. As a concrete example, we study a local relativistic field theory where a stable particle can capture a light quantum and form a quasi-stable state. As expected, to such a stable particle correspond energy eigenstates of the full theory, as is shown explicitly by using a dressed particle formalism at first order in perturbation theory. We derive an effective model of detector (at rest) where the stable particle and the quasi-stable configurations correspond to the two internal levels, "ground" and "excited", of the detector.Comment: 13 pages, references added, final versio

A Structural Domain Mediates Attachment of Ethanolamine Phosphoglycerol to Eukaryotic Elongation Factor 1A in Trypanosoma brucei

Ethanolamine phosphoglycerol (EPG) represents a protein modification that so far has only been found in eukaryotic elongation factor 1A (eEF1A). In mammals and plants, EPG is covalently attached to two conserved glutamate residues located in domains II and III of eEF1A. In contrast, Trypanosoma brucei eEF1A contains a single EPG attached to Glu362 in domain III. The sequence and/or structural requirements for covalent linkage of EPG to eEF1A have not been determined for any organism. Using a combination of biosynthetic labelling of parasites with tritiated ethanolamine and mass spectrometry analyses, we demonstrate that replacement of Glu362 in T. brucei eEF1A by site-directed mutagenesis prevents EPG attachment, whereas single or multiple amino acid substitutions around the attachment site are not critical. In addition, by expressing a series of eEF1A deletion mutants in T. brucei procyclic forms, we demonstrate that a peptide consisting of 80 amino acids of domain III of eEF1A is sufficient for EPG attachment to occur. Furthermore, EPG addition also occurs if domain III of eEF1A is fused to a soluble reporter protein. To our knowledge, this is the first report addressing amino acid sequence, or structure, requirements for EPG modification of eEF1A in any organism. Using T. brucei as a model organism, we show that amino acid substitutions around the modification site are not critical for EPG attachment and that a truncated version of domain III of eEF1A is sufficient to mediate EPG addition

Malaria Vaccine Development: Are Bacterial Flagellin Fusion Proteins the Bridge between Mouse and Humans?

In the past 25 years, the development of an effective malaria vaccine has become one of the biggest riddles in the biomedical sciences. Experimental data using animal infection models demonstrated that it is possible to induce protective immunity against different stages of malaria parasites. Nonetheless, the vast body of knowledge has generated disappointments when submitted to clinical conditions and presently a single antigen formulation has progressed to the point where it may be translated into a human vaccine. In parallel, new means to increase the protective effects of antigens in general have been pursued and depicted, such as the use of bacterial flagellins as carriers/adjuvants. Flagellins activate pathways in the innate immune system of both mice and humans. The recent report of the first Phase I clinical trial of a vaccine containing a Salmonella flagellin as carrier/adjuvant may fuel the use of these proteins in vaccine formulations. Herein, we review the studies on the use of recombinant flagellins as vaccine adjuvants with malarial antigens in the light of the current state of the art of malaria vaccine development. The available information indicates that bacterial flagellins should be seriously considered for malaria vaccine formulations to the development of effective human vaccines

Co-infection with Trypanosoma cruzi protects mice against early death by neurological or pulmonary disorders induced by Plasmodium berghei ANKA

Objective: the objective of this study was to investigate whether the infection of C57BL/ 6 mice by P. berghei ANKA, which causes severe malaria, was modulated by co-infection with Trypanosoma cruzi.Methods: Groups of C57BL/ 6 mice were infected either with P. berghei ANKA, T. cruzi strain G, or with both parasites. the presence of parasites was checked by microscopic examination of blood samples. Symptoms of neurological or respiratory disorders, as well as mortality, were registered. Breakdown of the blood brain barrier was determined by injecting the dye Evans blue. Histological sections of the lung were prepared and stained with hematoxilin-eosin.Results: All mice infected only with P. berghei ANKA died within 7-11 days post-infection, either with symptoms of cerebral malaria or with respiratory abnormalities. the animals co- infected with T. cruzi strain G survived longer, without any of the referred to symptoms. Protection against the early death by severe malaria was effective when mice were given T. cruzi 15 days before P. berghei inoculation. Breakdown of the blood brain barrier and extensive pulmonary oedema, caused by malaria parasites, were much less pronounced in co- infected mice. the degree of protection to severe malaria and early death, conferred by co- infection with T. cruzi, was comparable to that conferred by treatment with anti-CD8 antibodies.Conclusion: Co-infection with T. cruzi protects C57BL/ 6 against the early death by malaria infection, by partially preventing either the breakdown of the blood brain, and cerebral malaria as a consequence, or the pulmonary oedema.Universidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morfol, São Paulo, BrazilUniv Estadual Campinas, Inst Biol, Dept Parasitol, Campinas, SP, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morfol, São Paulo, BrazilWeb of Scienc

Determination of polychlorinated biphenyls in brazilian breast milk samples using solid-phase microextraction and gas chromatography-electron capture detection

A method for the determination of polychlorinated biphenyls (PCB) in breast milk was developed and applied to evaluate the contamination of samples that proceed from four Brazilian cities. PCB were extracted by Solid-Phase Microextraction and analyzed by Gas Chromatography with Electron Capture Detector. The figures of merit studied were linearity (to 16 µg L-1, r > 0.9884), precision (RSD 0,9884), precisão (RSD < 12%, n = 5), recuperação (71 a 127%) e limite de quantificação (entre 0,45 e 2,42 µg L-1). A análise das vinte amostras revelou níveis de PCB acima de 11,8 µg L-1 na região metropolitana de São Paulo, sendo o PCB 153 encontrado em todas essas amostras. Em Vitória/ES e Florianópolis/SC foram encontrados PCB em 100 e 60% das amostras, respectivamente. Nenhuma contaminação foi detectada nas amostras do Rio Branco/Acre. Sendo assim, uma alta correlação entre a contaminação dessas amostras e o nível de industrialização da região foi encontrada.502509Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Pathophysiological Mechanisms In Gaseous Therapies For Severe Malaria.

Over 200 million people worldwide suffer from malaria every year, a disease that causes 584,000 deaths annually. In recent years, significant improvements have been achieved on the treatment of severe malaria, with intravenous artesunate proving superior to quinine. However, mortality remains high at 8% in children and 15% in adults in clinical trials, and even worse in the case of cerebral malaria (18% and 30%, respectively). Moreover, some individuals who do not succumb to severe malaria present long-term cognitive deficits. These observations indicate that strategies focused only on parasite killing fail to prevent neurological complications and deaths associated with severe malaria, possibly because clinical complications are associated in part with a cerebrovascular dysfunction. Consequently, different adjunctive therapies aimed at modulating malaria pathophysiological processes are currently being tested. However, none of these therapies has shown unequivocal evidence in improving patients' clinical status. Recently, key studies have shown that gaseous therapies based mainly on nitric oxide (NO), carbon monoxide (CO) and hyperbaric (pressurized) oxygen (HBO) alter vascular endothelium dysfunction and modulate host immune response to infection. Considering gaseous administration as a promising adjunctive treatment against severe malaria cases, we review here the pathophysiological mechanisms and the immunological aspects of such therapies.8