Experimental infection with the Toxoplasma gondii ME-49 strain in the Brazilian BR-1 mini pig is a suitable animal model for human toxoplasmosis

Toxoplasma gondii causes toxoplasmosis, a worldwide disease. Experimentation with pigs is necessary for the development of new therapeutic approaches to human diseases. BR-1 mini pigs were intramuscularly infected with T. gondii with tachyzoites (RH strain) or orally infected with cysts (ME-49 strain). Haematology and serum biochemistry were analysed and buffy coat cells were inoculated in mice to determine tachyzoite circulation. No alterations were observed in erythrocyte and platelet values; however, band neutrophils increased seven days after infection with ME-49. Serology of the mice inoculated with pig blood leucocytes revealed circulating ME-49 or RH strain tachyzoites in the pigs' peripheral blood at two and seven or nine days post-infection. The tachyzoites were also directly observed in blood smears from the infected pigs outside and inside leucocytes for longer periods. Alanine-aminotransferase was high at days 21 and 32 in the RH infected pigs. After 90 days, the pigs were euthanised and their tissue samples were processed and inoculated into mice. The mice serology revealed the presence of parasites in the hearts, ileums and mesenteric lymph nodes of the pigs. Additionally, cysts in the mice were only observed after pig heart tissue inoculation. The infected pigs presented similar human outcomes with relatively low pathogenicity and the BR-1 mini pig model infected with ME-49 is suitable to monitor experimental toxoplasmosis.

Immunological response to re-infections with clones of the Colombian strain of Trypanosoma cruzi with different degrees of virulence: influence on pathological features during chronic infection in mice

Re-infections with Trypanosoma cruzi are an aggravating factor for Chagas disease morbidity. The Colombian strain of T. cruzirepresents multiclonal populations formed by clonally propagating organisms with different tropisms and degrees of virulence. In the present study, the influence of successive inoculations with clones of the Colombian strain, exhibiting different degrees of virulence, on chronic myocarditis and the humoral and cellular immune responses (Col-C1 high virulence, Col-C8 medium virulence and Col-C5 low virulence) were demonstrated. Mice from three groups with a single infection were evaluated during the acute (14th-30th day) and chronic phases for 175 days. An immunofluorescence assay, ELISA and delayed type hypersensitivity (DTH) cutaneous test were also performed. Mice with a triple infection were studied on the 115th-175th days following first inoculation. The levels of IgM and IgG2a were higher in the animals with a triple infection. DTH showed a higher intensity in the inflammatory infiltrate based on the morphometric analysis during a 48 h period of the triple infection and at 24 h with a single infection. The histopathology of the heart demonstrated significant exacerbation of cardiac inflammatory lesions confirmed by the morphometric test. The humoral responses indicate a reaction to the triple infection, even with clones of the same strain.

The neurobiological basis of prefrontal cortex impairment in the phencyclidine model of schizophrenia : convergent reduction of synaptic glutamate release, energy metabolism and cognitive performance

RÉSUMÉ : Le traitement répété à la phencyclidine (PCP), un bloqueur du récepteur NMDA (NMDAR), reproduit chez les rongeurs une partie de la symptomatologie typique de la schizophrénie. Le blocage prolongé du NMDAR par la PCP mime une hypofunction du NMDAR, une des principales altérations supposées exister dans les cerveaux des patients schizophréniques. Le but de notre étude était d'examiner les conséquences neurochimiques, métaboliques et fonctionnelles du traitement répété à la phencyclidine in vivo, au niveau du cortex préfrontal (cpf), une région cérébrale qui joue un rôle dans les déficits cognitifs observés chez les patients schizophréniques. Pour répondre à cette question, les rats ou les souris ont reçu chaque jour une injection soit de PCP (5 mg/kg), soit de solution saline, pendant 7 ou 14 jours. Les animaux ont ensuite été sacrifiés au moins 24 heures après le dernier traitement. Des tranches aiguës du cpf ont été préparées rapidement, puis stimulées avec une concentration élevée de KCI, de manière à induire une libération de glutamate à partir des terminaisons synaptiques excitatrices. Les résultats montrent que les tranches du cpf des animaux traités à la PCP ont libéré une quantité de glutamate significativement inférieure par rapport à celles des animaux contrôle. Ce déficit de libération a persisté 72 heures après la fin du traitement, tandis qu'il n'était pas observé dans le cortex visuel primaire, une autre région corticale. En outre, le traitement avec des antipsychotiques, l'halopéridol ou l'olanzapine, a supprimé le déficit induit par la PCP. Le même déficit de libération a été remarqué sur des synaptosomes obtenus à partir du cpf des animaux traités à la phenryclidine. Cette observation indique que la PCP induit une modification plastique adaptative du mécanisme qui contrôle la libération du glutamate dans les terminaisons synaptiques. Nous avons découvert que cette modification implique la sous-régulation d'un NMDAR présynaptique, qui serait doué d'un rôle d'autorécepteur stimulateur de la libération du glutamate. Grâce à des tests comportementaux conduits en parallèle et réalisés pour évaluer la fonctionnalité du cpf, nous avons observé chez les souris traitées à la PCP une flexibilité comportementale réduite lors d'un test de discrimination de stimuli visuels/tactiles. Le déficit cognitif était encore présent 4 jours après la dernière administration de PCP. La technique de l'autoradiographie quantitative du [14C]2-deoxyglucose a permis d'associer ce déficit à une réduction de l'activité métabolique cérébrale pendant le déroulement du test, particulièrement au niveau du cpf. Dans l'ensemble, nos résultats suggèrent que le blocage prolongé du NMDAR lors de l'administration répétée de PCP produit un déficit de libération du glutamate au niveau des terminaisons synaptiques excitatrices du cpf. Un tel déficit pourrait être provoqué par la sousrégulation d'un NMDAR présynaptique, qui aurait une fonction de stimulateur de libération; la transmission excitatrice du cpf s'en trouverait dans ce cas réduite. Ce résultat est en ligne avec l'activité métabolique et fonctionnelle réduite du cpf et l'observation de déficits cognitifs induits lors de l'administration de la PCP. ABSTRACT : Sub-chronic treatment with phencyclidine (PCP), an NMDA receptor (NMDAR) channel blocker, reproduces in rodents part of the symptomatology associated to schizophrenia in humans. Prolonged pharmacological blockade of NMDAR with PCP mimics NMDAR hypofunction, one of the main alterations thought to take place in the brains of schizophrenics. Our study was aimed at investigating the neurochemical, metabolic and behavioral consequences of repeated PCP administration in vivo, focusing on the functioning of the prefrontal cortex (pfc), a brain region highly relevant for the cognitive deficits observed in schizophrenic patients. Rats or mice received a daily administration of either PCP (5 mg/kg) or saline for 7 or 14 days. At least 24 hours after the last treatment the animals were sacrificed. Acute slices of the pfc were quickly prepared and challenged with high KCl to induce synaptic glutamate release. Pfc slices from PCP-treated animals released significantly less glutamate than slices from salinetreated animals. The deficit persisted 72 hours after the end of the treatment, while it was not observed in another cortical region: the primary visual cortex. Interestingly, treatment with antipsychotic drugs, either haloperidol or olanzapine, reverted the glutamate release defect induced by PCP treatment. The same release defect was observed in synaptosomes prepared from the pfc of PCP-treated animals, indicating that PCP induces a plastic adaptive change in the mechanism controlling glutamate release in the glutamatergic terminals. We discovered that such change most likely involves the down-regulation of a newly identified, pre-synaptic NMDAR with stimulatory auto-receptor function on glutamate release. In parallel sets of behavioral experiments challenging pfc function, mice sub-chronically treated with PCP displayed reduced behavioral flexibility (reversal learning) in a visual/tactile-cued discrimination task. The cognitive deficit was still evident 4 days after the last PCP administration and was associated to reduced brain metabolic activity during the performance of the behavioral task, notably in the pfc, as determined by [14C]2-deoxyglucose quantitative autoradiography. Clverall, our findings suggest that prolonged NMDAR blockade by repeated PCP administration results in a defect of glutamate release from excitatory afferents in the pfc, possibly ascribed to down-regulation of apre-synaptic stimulatory NMDAR. Deficient excitatory neurotransmission in the pfc is consistent with the reduced metabolic and functional activation of this area and the observed PCP-induced cognitive deficits.

Pattern of cytokine and chemokine production by THP-1 derived macrophages in response to live or heat-killed Mycobacterium bovis bacillus Calmette-Guérin Moreau strain

Tuberculosis has great public health impact with high rates of mortality and the only prophylactic measure for it is the Mycobacterium bovisbacillus Calmette-Guérin (BCG) vaccine. The present study evaluated the release of cytokines [interleukin (IL)-1, tumour necrosis factor and IL-6] and chemokines [macrophage inflammatory protein (MIP)-1α and MIP-1β] by THP-1 derived macrophages infected with BCG vaccine obtained by growing mycobacteria in Viscondessa de Moraes Institute medium medium (oral) or Sauton medium (intradermic) to compare the effects of live and heat-killed (HK) mycobacteria. Because BCG has been reported to lose viability during the lyophilisation process and during storage, we examined whether exposing BCG to different temperatures also triggers differences in the expression of some important cytokines and chemokines of the immune response. Interestingly, we observed that HK mycobacteria stimulated cytokine and chemokine production in a different pattern from that observed with live mycobacteria.

Association of irisin with fat mass, resting energy expenditure, and daily activity in conditions of extreme body mass index.

FNDC5/irisin has been recently postulated as beneficial in the treatment of obesity and diabetes because it is induced in muscle by exercise, increasing energy expenditure. However, recent reports have shown that WAT also secretes irisin and that circulating irisin is elevated in obese subjects. The aim of this study was to evaluate irisin levels in conditions of extreme BMI and its correlation with basal metabolism and daily activity. The study involved 145 female patients, including 96 with extreme BMIs (30 anorexic (AN) and 66 obese (OB)) and 49 healthy normal weight (NW). The plasma irisin levels were significantly elevated in the OB patients compared with the AN and NW patients. Irisin also correlated positively with body weight, BMI, and fat mass. The OB patients exhibited the highest REE and higher daily physical activity compared with the AN patients but lower activity compared with the NW patients. The irisin levels were inversely correlated with daily physical activity and directly correlated with REE. Fat mass contributed to most of the variability of the irisin plasma levels independently of the other studied parameters. Conclusion. Irisin levels are influenced by energy expenditure independently of daily physical activity but fat mass is the main contributing factor.

Genomic analysis of a nontoxigenic, invasive Corynebacterium diphtheriae strain from Brazil

We report the complete genome sequence and analysis of an invasive Corynebacterium diphtheriae strain that caused endocarditis in Rio de Janeiro, Brazil. It was selected for sequencing on the basis of the current relevance of nontoxigenic strains for public health. The genomic information was explored in the context of diversity, plasticity and genetic relatedness with other contemporary strains.

Draft genome sequence of Bacillus thuringiensis 147, a Brazilian strain with high insecticidal activity

Bacillus thuringiensisis a ubiquitous Gram-positive and sporulating bacterium. Its crystals and secreted toxins are useful tools against larvae of diverse insect orders and, as a consequence, an alternative to recalcitrant chemical insecticides. We report here the draft genome sequence ofB. thuringiensis147, a strain isolated from Brazil and with high insecticidal activity. The assembled genome contained 6,167,994 bp and was distributed in seven replicons (a chromosome and 6 plasmids). We identified 12 coding regions, located in two plasmids, which encode insecticidal proteins.

International regimes as knowledge syndicates? Energy and trends of global governance

El poder de l'Estat i la sobirania tradicional s'està deteriorant de manera constant, sobretot en termes de la provisió de certs béns públics fonamentals. Els Estats, en particular, són incapaços de manejar el coneixement i la informació que és essencial per mantenir la competitivitat i la sostenibilitat en una economia interdependent. Estructures fiables de la governança mundial i la cooperació internacional estan lluny de ser establertes. Energia com a problema a les agendes p dels governs, les empreses privades i la societat civil és un exemple manifest d'aquesta dinàmica.. L'actual sistema de governança mundial d'energia implica accions polítiques disperses per actors divers. L'Agència Internacional de l'Energia té un paper destacat, però està debilitat per la seva composició limitada i basada en el coneixement- epistèmic en lloc del material o executiu. Aquest treball sosté que ni la mida ni nombre de membres disponibles estan dificultant la governabilitat mundial d'energia. Més aviat, l'energia és una sèrie de béns públics que es troben als llimbs, on els estats no poden pagar la seva disposició, així com els diversos interessos impedir l'establiment d'una autoritat internacional. Després de la introducció de la teoria del règim internacional i el concepte de coneixement basats en les comunitats epistèmiques, l'article revisa l'estat actual de la governabilitat de l'energia mundia. A continuació es presenta una comparació d'aquesta estructura amb els règims de govern nacional i regional, d'una banda, i amb règims globals ambientals i de salut, de l'altra

Perspectives on the green construction of the new European Energy Policy

The EU has been one of the main actors involved in the construction process of an international climate change regime, adopting it as an identity sign in the international arena. This activism has reverted in the European political agenda and in the one of its Members States. Therefore, climate change has become a driver for the EU growing participation in energy policy and for its governance evolution. In this context, much attention has been paid to the climate and energy policies integration agreed after the 2007 spring European Council. Apparently, this decision meant a decisive step towards the incorporation of the environmental variable in the energy policy-making. Moreover, the Action Plan [2007-2009] “Energy Policy for Europe” outlined priority actions in a variety of energy-related areas, implying the new European Energy Policy commencement. Against this background, there is still much left to understand about its formulation and its further development. Rooted on the Environmental Policy Integration approach, this paper traces the increasing proximity between environment and energy policies in order to understand the green contribution to the European Energy Policy construction.

The EU ‘2020 Energy Initiative’: The post-Lisbon pattern of change in EU energy policy

El novembre de 2010, la Comissió Europea ha finalment donat a conèixer la seva "Energia 2020 Comunicació", un document estratègic en el marc més ampli del programa "Europa 2020". Una estratègia per al desenvolupament sostenible intel · ligent, i creixement inclusiu posa les bases d'un nou enfocament a la política d'energia a la UE. En el marc d'Europa 2020, la Iniciativa d'Energia recopila els resultats que ja s'han obtingut a través de la Estratègia de Lisboa 2000-2010, s'identifiquen les deficiències del passat i i introdueix nous objectius ambiciosos per a la UE en matèria de política energètica.

The Strategic value of European renewable energy promotion policy

Encara falta per fer possible una transformació estratègica d'Europa del sistema d'energia, però el que és de la mateixa importància com a objectius a llarg termini de la FER i Reduccions de GEH són vinculants i forts objectius d'eficiència energètica, no només per 2020, però també per al 2030, 2040 i 2050, com aquesta força ajudaria a fixar l'augment de les energies renovables en el total d'energia consum i per reduir el total Emissions de GEH d'Europa en general, i les del sector de l'energia en particular, encara sent un dels majors emissors de gasos d'efecte hivernacle de tots els sectors. La refosa Directiva, prevista per 2011/12 ha de ser un bones finestres d'oportunitat per finalment establir objectius vinculants d'eficiència energètica, l'únic pilar que encara falta en la força energia interdependents i estratègia sobre el clima de la UE, basat en la reducció de gasos d'efecte hivernacle i i l'eficiència energètica.

Energy-nitrogen balances and protein turnover in small and appropriate for gestational age low birthweight infants.

The aim of the present study was to compare, under the same nursing conditions, the energy-nitrogen balance and the protein turnover in small for gestational age (SGA) and appropriate for gestational age (AGA) low birthweight infants. We compared 8 SGA's (mean +/- s.d.: gestational age 35 +/- 2 weeks, birthweight 1520 +/- 330 g) to 11 AGA premature infants (32 +/- 2 weeks, birthweight 1560 +/- 240 g). When their rate of weight gain was above 15 g/kg/d (17.6 +/- 3.0 and 18.2 +/- 2.6 g/kg/d, mean postnatal age 18 +/- 10 and 20 +/- 9 d respectively) they were studied with respect to their metabolizable energy intake, their energy expenditure, their energy and protein gain and their protein turnover. Energy balance was assessed by the difference between metabolizable energy and energy expenditure as measured by indirect calorimetry. Protein gain was calculated from the amount of retained nitrogen. Protein turnover was estimated by a stable isotope enrichment technique using repeated nasogastric administration of 15N-glycine for 72 h. Although there was no difference in their metabolizable energy intakes (110 +/- 12 versus 108 +/- 11 kcal/kg/d), SGA's had a higher rate of resting energy expenditure (64 +/- 8 versus 57 +/- 8 kcal/kg/d, P less than 0.05). Protein gain and composition of weight gain was very similar in both groups (2.0 +/- 0.4 versus 2.1 +/- 0.4 g protein/kg/d; 3.5 +/- 1.1 versus 3.3 +/- 1.4 g fat/kg/d in SGA's and AGA's respectively). However, the rate of protein synthesis was significantly lower in SGA's (7.7 +/- 1.6 g/kg/d) as compared to AGA's (9.7 +/- 2.8 g/kg/d; P less than 0.05). It is concluded that SGA's have a more efficient protein gain/protein synthesis ratio since for the same weight and protein gains, SGA's show a 20 per cent slower protein turnover. They might therefore tolerate slightly higher protein intakes. Postconceptional age seems to be an important factor in the regulation of protein turnover.

Complete genome of a dengue virus serotype 4 strain from Amazonas, Brazil

Dengue virus (DENV) infections represent a significant concern for public health worldwide, being considered as the most prevalent arthropod-borne virus regarding the number of reported cases. In this study, we report the complete genome sequencing of a DENV serotype 4 isolate, genotype II, obtained in the city of Manaus, directly from the serum sample, applying Ion Torrent sequencing technology. The use of a massive sequencing technology allowed the detection of two variable sites, one in the coding region for the viral envelope protein and the other in the nonstructural 1 coding region within viral populations.

Complete genome of the multidrug-resistant Acinetobacter baumannii strain KBN10P02143 isolated from Korea

Acinetobacter baumannii, a strictly aerobic, non-fermentative, Gram-negative coccobacillary rod-shaped bacterium, is an opportunistic pathogen in humans. We recently isolated a multidrug-resistant A. baumannii strain KBN10P02143 from the pus sample drawn from a surgical patient in South Korea. We report the complete genome of this strain, which consists of 4,139,396 bp (G + C content, 39.08%) with 3,868 protein-coding genes, 73 tRNAs and six rRNA operons. Identification of the genes related to multidrug resistance from this genome and the discovery of a novel conjugative plasmid will increase our understanding of the pathogenicity associated with this species.

Multi-modal distraction: insights from children's limited attention.

How does the multi-sensory nature of stimuli influence information processing? Cognitive systems with limited selective attention can elucidate these processes. Six-year-olds, 11-year-olds and 20-year-olds engaged in a visual search task that required them to detect a pre-defined coloured shape under conditions of low or high visual perceptual load. On each trial, a peripheral distractor that could be either compatible or incompatible with the current target colour was presented either visually, auditorily or audiovisually. Unlike unimodal distractors, audiovisual distractors elicited reliable compatibility effects across the two levels of load in adults and in the older children, but high visual load significantly reduced distraction for all children, especially the youngest participants. This study provides the first demonstration that multi-sensory distraction has powerful effects on selective attention: Adults and older children alike allocate attention to potentially relevant information across multiple senses. However, poorer attentional resources can, paradoxically, shield the youngest children from the deleterious effects of multi-sensory distraction. Furthermore, we highlight how developmental research can enrich the understanding of distinct mechanisms controlling adult selective attention in multi-sensory environments.