Distinct roles for FOXP3(+) and FOXP3(-) CD4(+) T cells in regulating cellular immunity to uncomplicated and severe plasmodium falciparum Malaria

Failure to establish an appropriate balance between pro- and anti-inflammatory immune responses is believed to contribute to pathogenesis of severe malaria. To determine whether this balance is maintained by classical regulatory T cells (CD4+ FOXP3+ CD127−/low; Tregs) we compared cellular responses between Gambian children (n = 124) with severe Plasmodium falciparum malaria or uncomplicated malaria infections. Although no significant differences in Treg numbers or function were observed between the groups, Treg activity during acute disease was inversely correlated with malaria-specific memory responses detectable 28 days later. Thus, while Tregs may not regulate acute malarial inflammation, they may limit memory responses to levels that subsequently facilitate parasite clearance without causing immunopathology. Importantly, we identified a population of FOXP3−, CD45RO+ CD4+ T cells which coproduce IL-10 and IFN-γ. These cells are more prevalent in children with uncomplicated malaria than in those with severe disease, suggesting that they may be the regulators of acute malarial inflammation

The position of graptolites within Lower Palaeozoic planktic ecosystems.

An integrated approach has been used to assess the palaeoecology of graptolites both as a discrete group and also as a part of the biota present within Ordovician and Silurian planktic realms. Study of the functional morphology of graptolites and comparisons with recent ecological analogues demonstrates that graptolites most probably filled a variety of niches as primary consumers, with modes of life related to the colony morphotype. Graptolite coloniality was extremely ordered, lacking any close morphological analogues in Recent faunas. To obtain maximum functional efficiency, graptolites would have needed varying degrees of coordinated automobility. A change in lifestyle related to ontogenetic changes was prevalent within many graptolite groups. Differing lifestyle was reflected by differing reproductive strategies, with synrhabdosomes most likely being a method for rapid asexual reproduction. Direct evidence in the form of graptolithophage 'coprolitic' bodies, as well as indirect evidence in the form of probable defensive adaptations, indicate that graptolites comprised a food item for a variety of predators. Graptolites were also hosts to a variety of parasitic organisms and provided an important nutrient source for scavenging organisms

Comparison of pharmacopeial statistical methods applied in microbiological assay for antibiotics potency determination using parallel lines and three-dose level

Pharmaceutical equivalence studies, useful for checking the interchangeability of generic medicines and their respective innovator medicines, have been carried out in Brazil since 1999, as a consequence of the establishment of the generic medicine policy. For medicines containing antibiotics, microbiological assays are often the most appropriate method. However, the statistical methods applied in these assays are not widely known due to the difficult access to official codes and/or little knowledge of the statistical tools of analysis. Thus, the aim of this work was to compare the statistical methods for determining the potency of antibiotics through the cylinder-plate method using parallel lines and a three-dose level model, as described in the Brazilian Pharmacopeia (4th edition, 1988), British Pharmacopoeia 2011, European Pharmacopoeia (7th edition), The International Pharmacopoeia (4th edition), and United States Pharmacopeia (34th edition). The assay is illustrated with the antibiotic ofloxacin, and details on orthogonal coefficients, normality test, homogeneity of variance test, and detection of outliers are discussed. The calculations obtained by statistical analyses from different pharmacopeias lead to the same final interpretation. In practice, with the availability of alternative pharmacopeial methods, the analyst can choose the most appropriate statistical calculation to be used.Os estudos de equivalência farmacêutica, úteis na verificação da intercambialidade entre os medicamentos genéricos e respectivos medicamentos de referência, têm sido realizados no Brasil desde 1999, como consequência do estabelecimento da política de medicamentos genéricos. Para medicamentos contendo antibióticos, os ensaios microbiológicos são, muitas vezes, o método mais adequado. Entretanto, os métodos estatísticos aplicados nesses ensaios não são amplamente conhecidos devido à dificuldade de acesso aos compêndios oficiais e/ou pouca compreensão das ferramentas estatísticas de análises. Portanto, o objetivo desse trabalho foi comparar os métodos estatísticos para determinação de potência de antibióticos pelo delineamento por retas paralelas e três níveis de doses, descritos nas farmacopeias Brasileira 4. ed. (1988), Britânica 2011, Europeia 7. ed., Internacional 4. ed. e na Farmacopeia dos Estados Unidos 34. ed. (2011). O ensaio é exemplificado com o antibiótico ofloxacino e detalhes sobre coeficientes ortogonais, teste de normalidade, teste de homogeneidade de variância e detecção de outliers são discutidos. Os cálculos obtidos pelas análises estatísticas segundo as diferentes farmacopeias resultaram na mesma interpretação final. Na prática, métodos farmacopéicos alternativos permitem ao analista a escolha do cálculo estatístico mais apropriado a ser utilizado

Does congenital deafness affect the structural and functional architecture of primary visual cortex?

Deafness results in greater reliance on the remaining senses. It is unknown whether the cortical architecture of the intact senses is optimized to compensate for lost input. Here we performed widefield population receptive field (pRF) mapping of primary visual cortex (V1) with functional magnetic resonance imaging (fMRI) in hearing and congenitally deaf participants, all of whom had learnt sign language after the age of 10 years. We found larger pRFs encoding the peripheral visual field of deaf compared to hearing participants. This was likely driven by larger facilitatory center zones of the pRF profile concentrated in the near and far periphery in the deaf group. pRF density was comparable between groups, indicating pRFs overlapped more in the deaf group. This could suggest that a coarse coding strategy underlies enhanced peripheral visual skills in deaf people. Cortical thickness was also decreased in V1 in the deaf group. These findings suggest deafness causes structural and functional plasticity at the earliest stages of visual cortex

Resistance of Brazilian diamondback moth populations to insecticides

Plutella xylostella is a recurring pest on cruciferous crops around the world. In Brazil, it typically requires large number of insecticide sprays, which may lead to fast evolution of resistance. The aim of this study was to assess the susceptibility of Brazilian diamondback moth populations to the insecticides abamectin, deltamethrin, and spinosad. Leaf dip bioassays were used to determine mortality data obtained after 48 h of exposure to insecticides and subjected to Probit analysis. The population from Bonito, state of Pernambuco, Brazil, had the highest toxicity ratio (20.2 - fold) to abamectin compared to the reference population. The LC50 values for deltamethrin ranged from 85.2 to 360.1 mg L-1, demonstrating a high survival of populations in relation to this insecticide field dose rate (7.5 mg L-1). The toxicity ratios of the estimated LC50s, however, were very low (varying from 2.2 - to 4.2 - fold). Most populations exhibited toxicity ratios for spinosad, ranging from 2.3 - to 5.1 - fold, while both the LC50 and LC95 values reflected a high susceptibility to the spinosad field dosage (120 mg L-1). Only the Bonito - PE population resisted to abamectin, while all P. xylostella populations were resistant to deltamethrin, but particularly susceptible to spinosad because of the absence of selection pressure with it in these areas.Plutella xylostella é uma praga recorrente em brássicas de todo o mundo. No Brasil, normalmente exige grande número de pulverizações de inseticidas, que pode levar à rápida evolução da resistência. Avaliou-se a suscetibilidade de populações brasileiras da traça das crucíferas aos inseticidas abamectina, deltametrina e espinosade. Bioensaios de imersão de folhas foram utilizados para determinar a mortalidade, sendo os dados obtidos após 48 h de exposição aos inseticidas e submetidos à análise de Probit. A população de Bonito-PE apresentou a maior razão de toxicidade (20,2 vezes) para abamectina em relação à população de referência. Os valores de CL50s para deltametrina variaram entre 85,2 - 360,1 mg L-1, demonstrando alta sobrevivência das populações a este inseticida com relação à dose de campo (7,5 mg L-1). Entretanto, as razões de toxicidade das CL50 estimadas foram muito baixas (variando de 2,2 a 4,2 vezes). A maioria das populações apresentou razões de toxicidade para espinosade, variando de 2,3 para 5,1 vezes, embora os valores de CL demonstram alta suscetibilidade delas à dose de campo para espinosade (120 mg L-1). Apenas a população de Bonito PE apresentou resistência a abamectina, enquanto todas as populações de P. xylostella estão resistentes a deltametrina, mas suscetíveis ao espinosade particularmente devido à ausência de pressão de seleção com este nestas áreas