Regulatory CD4+ CD25+ Foxp3+ T cells expand during experimental Plasmodium infection but do not prevent cerebral malaria

Pathogenic CD8+ T cells are implicated in the physiopathological mechanisms leading to experimental cerebral malaria (CM) in Plasmodium berghei ANKA (PbA) infected mice. Therefore, we hypothesised that in CM susceptible mice the neuropathology could be, at least in part, the result of an inefficient control of pathogenic effector T cells by CD4+ CD25+ Treg cells. Remarkably, the number of CD4+ CD25high T cells expressing Foxp3 increased in the spleen during the course of infection. These cells displayed an activated phenotype and consistent with that, CD4+ CD25high Treg cells isolated from PbA-infected mice showed an enhanced regulatory activity in vitro. Surprisingly, these cells do not migrate to the brain at the time of neurological symptoms as the conventional CD4+ T cells do. CM was not exacerbated in anti-CD25 treated mice when infected with PbA one month after treatment, even if splenic CD8+ T cells expressing CD69 increased in these mice. Taken together, these results show that P. berghei infection leads to an increase of the number of splenic CD4+ CD25high Treg cells exhibiting in vitro suppressive function, but they do not seem to be involved in vivo in the protection against CM.     

PP1-Mediated Dephosphorylation of Lgl Controls Apical-basal Polarity

1. Download high-res image (271KB)
2. Download full-size image

     

Lack of lactate-proton symport activity in pck1 mutants of Saccharomyces cerevisiae

Abstract Mutants of Saccharomyces cerevisiae without phosphoenolpyruvate carboxykinase activity showed no measurable lactate proton symport, while mutants without fructose-1,6-bisphosphatase had normal transport activity. Incubation of a pck1 mutant, under derepression conditions in the presence of glycerol, restored the activity of the lactate-proton symport, with identical kinetic characteristics to that in the wild-type. For efficient lactate-proton symport activity, not only is an external inducer such as lactic acid needed, but also a molecule derived from the acid metabolism may be necessary.     

Synthesis of novel purine nucleosides towards a selective inhibition of human butyrylcholinesterase

The search for new and potent cholinesterase inhibitors is an ongoing quest mobilizing many organic chemistry groups around the world as these molecules have been shown to treat the late symptoms of Alzheimer’s disease as well as to act as neuroprotecting agents. In this work, we disclose the synthesis of novel 2-acetamidopurine nucleosides and, for the first time, regioselective N⁷-glycosylation with 2-acetamido-6-chloropurine, promoted by trimethylsilyl triflate, was accomplished by tuning the reaction conditions (acetonitrile as solvent, 65 °C, 5 h) starting from 1-acetoxy bicyclic glycosyl donors, or by direct coupling of a methyl glucopyranoside with the nucleobase to obtain only N⁷ nucleosides in reasonable yield (55–60%). The nucleosides as well as their sugar precursors were screened for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition. While none of the compounds tested inhibited AChE, remarkably, some of the N⁷ nucleosides and sugar bicyclic derivatives showed potent inhibition towards BChE. Nanomolar inhibition was obtained for one compound competing well with rivastigmine, a drug currently in use for the treatment of Alzheimer’s disease. Experimental results showed that the presence of benzyl groups on the carbohydrate scaffold and the N⁷-linked purine nucleobase were necessary for strong BChE inactivation. A preliminary evaluation of the acute cytotoxicity of the elongated bicyclic sugar precursors and nucleosides was performed indicating low values, in the same order of magnitude as those of rivastigmine.     

On the edge of Bantu expansions: mtDNA, Y chromosome and lactase persistence genetic variation in southwestern Angola

Background

Ariids or sea catfishes are one of the two otophysan fish families (out of about 67 families in four orders) that inhabit mainly marine and brackish waters (although some species occur strictly in fresh waters). The group includes over 150 species placed in ~29 genera and two subfamilies (Galeichthyinae and Ariinae). Despite their global distribution, ariids are largely restricted to the continental shelves due in part to their specialized reproductive behavior (i.e., oral incubation). Thus, among marine fishes, ariids offer an excellent opportunity for inferring historical biogeographic scenarios. Phylogenetic hypotheses available for ariids have focused on restricted geographic areas and comprehensive phylogenies are still missing. This study inferred phylogenetic hypotheses for 123 ariid species in 28 genera from different biogeographic provinces using both mitochondrial and nuclear sequences (up to ~4 kb).

Results

While the topologies obtained support the monophyly of basal groups, up to ten genera validated in previous morphological studies were incongruent with the molecular topologies. New World ariines were recovered as paraphyletic and Old World ariines were grouped into a well-supported clade that was further divided into subclades mainly restricted to major Gondwanan landmasses. A general area cladogram derived from the area cladograms of ariines and three other fish groups was largely congruent with the geological area cladogram of Gondwana. Nonetheless, molecular clock estimations provided variable results on the timing of ariine diversification (~105-41 mya).

Conclusion

This study provides the most comprehensive phylogeny of sea catfishes to date and highlights the need for re-assessment of their classification. While from a topological standpoint the evolutionary history of ariines is mostly congruent with vicariance associated with the sequence of events during Gondwanan fragmentation, ambiguous divergence time estimations hinders assessing the vicariant hypothesis on a temporal framework. Further examination of ariid fossils might provide the basis for more accurate inferences on the timing of ariine diversification.     

Pherotypes are driving genetic differentiation within Streptococcus pneumoniae

Background  

The boundaries of bacterial species and the mechanisms underlying bacterial speciation are matters of intense debate. Theoretical studies have shown that recombination acts as a strong cohesive force preventing divergence in bacterial populations. Streptococcus pneumoniae populations have the telltale signs of high recombination with competence implicated as the major driving force behind gene exchange. Competence in S. pneumoniae is triggered by a quorum-sensing mechanism controlled by the competence-stimulating peptide pheromone.     

Automatic recognition and measurement of butterfly eyespot patterns

A favorite wing pattern element in butterflies that has been the focus of intense study in evolutionary and developmental biology, as well as in behavioral ecology, is the eyespot. Because the pace of research on these bull's eye patterns is accelerating we sought to develop a tool to automatically detect and measure butterfly eyespot patterns in digital images of the wings. We used a machine learning algorithm with features based on circularity and symmetry to detect eyespots on the images. The algorithm is first trained with examples from a database of images with two different labels (eyespot and non-eyespot), and subsequently is able to provide classification for a new image. After an eyespot is detected the radius measurements of its color rings are performed by a 1D Hough Transform which corresponds to histogramming. We trained software to recognize eyespot patterns of the nymphalid butterfly Bicyclus anynana but eyespots of other butterfly species were also successfully detected by the software.     

Divergent evolution of molecular markers during laboratory adaptation in Drosophila subobscura

The impact of genetic drift in population divergence can be elucidated using replicated laboratory experiments. In the present study we used microsatellite loci to study the genetic variability and differentiation of laboratory populations of Drosophila subobscura derived from a common ancestral natural population after 49 generations in the laboratory. We found substantial genetic variability in all our populations. The high levels of genetic variability, similar across replicated populations, suggest that careful maintenance procedures can efficiently reduce the loss of genetic variability in captive populations undergoing adaptation, even without applying active management procedures with conservation purposes, in organisms that generate a high number of offspring such as Drosophila. Nevertheless, there was a significant genetic differentiation between replicated populations. This shows the importance of genetic drift, acting through changes in allele frequencies among populations, even when major changes in the degree of genetic diversity in each population are not involved.