BDNF prevents NMDA‐induced toxicity in models of Huntington's disease: the effects are genotype specific and adenosine A2A receptor is involved

NMDA receptor‐mediated excitotoxicity is thought to play a pivotal role in the pathogenesis of Huntington's disease (HD). The neurotrophin brain‐derived neurotrophic factor (BDNF), which is also highly involved in HD and whose effects are modulated by adenosine A_2ARs, influences the activity and expression of striatal NMDA receptors. In electrophysiology experiments, we investigated the role of BDNF toward NMDA‐induced effects in HD models, and the possible involvement of A_2ARs. In corticostriatal slices from wild‐type mice and age‐matched symptomatic R6/2 mice (a model of HD), NMDA application (75 μM) induced a transient or a permanent (i.e., toxic) reduction of field potential amplitude, respectively. BDNF (10 ng/mL) potentiated NMDA effects in wild‐type, while it protected from NMDA toxicity in R6/2 mice. Both effects of BDNF were prevented by A_2AR blockade. The protective effect of BDNF against NMDA‐induced toxicity was reproduced in a cellular model of HD. These findings may have very important implications for the neuroprotective potential of BDNF and A_2AR ligands in HD.     

ADP-ribosylation of Translation Elongation Factor 2 by Diphtheria Toxin in Yeast Inhibits Translation and Cell Separation

Eukaryotic translation elongation factor 2 (eEF2) facilitates the movement of the peptidyl tRNA-mRNA complex from the A site of the ribosome to the P site during protein synthesis. ADP-ribosylation (ADP^R) of eEF2 by bacterial toxins on a unique diphthamide residue inhibits its translocation activity, but the mechanism is unclear. We have employed a hormone-inducible diphtheria toxin (DT) expression system in Saccharomyces cerevisiae which allows for the rapid induction of ADP^R-eEF2 to examine the effects of DT in vivo. ADP^R of eEF2 resulted in a decrease in total protein synthesis consistent with a defect in translation elongation. Association of eEF2 with polyribosomes, however, was unchanged upon expression of DT. Upon prolonged exposure to DT, cells with an abnormal morphology and increased DNA content accumulated. This observation was specific to DT expression and was not observed when translation elongation was inhibited by other methods. Examination of these cells by electron microscopy indicated a defect in cell separation following mitosis. These results suggest that expression of proteins late in the cell cycle is particularly sensitive to inhibition by ADP^R-eEF2.     

Integrin CD11c/CD18 α-Chain Phosphorylation Is Functionally Important

CD11c/CD18 (α_Xβ₂, p150/95, or complement receptor 4, CR4) is a monocyte/macrophage-enriched integrin that has been reported to bind to a variety of ligands. These include cell surface proteins, extracellular matrix proteins, and soluble ligands. The regulation of ligand binding to CD11c/CD18 has remained poorly understood. Previous work has shown that both α-chain and β-chain phosphorylations of CD11a/CD18 and CD11b/CD18 are needed for activity, but no corresponding studies on CD11c/CD18 have been performed. In this study, we have identified the phosphorylation site of CD11c as Ser-1158 and show that it is pivotal for adherence and phagocytosis.     

Very fine‐scale population genetic structure of sympatric asterinid sea stars with benthic and pelagic larvae: influence of mating system and dispersal potential

The present study investigated the fine‐scale population genetic structure of sympatric asterinid sea stars with contrasting modes of larval development (benthic versus pelagic). Parvulastra exigua lacks a dispersive life phase yet is one of the worlds most widely distributed and abundant sea stars, whereas Meridiastra calcar, a sea star with a dispersive larva, has a more limited regional scale distribution. Populations of P. exigua sampled from tide pools on three adjacent headlands showed significant genetic substructure (mitochodrial DNA control region) at fine spatial scales (tide pools < 300 m apart: F_ST = 0.249, P < 0.01; headlands 5–15 km apart: F_ST = 0.125, P = 0.04). As expected, M. calcar populations sampled from the same headlands did not exhibit significant genetic structuring (F_ST = 0.029, P = 0.14). The life‐history traits of P. exigua, a mixed mating system (selfing + outcrossing), pseudocopulation among closely‐related conspecifics, and an entirely benthic life cycle with a philopatric larva, undoubtedly influence its strong genetic structure across fine spatial scales. Localized genetic structure, especially at the very fine‐scale of tide pools, would not be detected in the more typical regional scale approaches adopted by most studies of marine invertebrate populations. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, ●●, ●●–●●.     

Brain changes in BDNF and S100B induced by ketogenic diets in Wistar rats

AimsWe investigated the effects of ketogenic diet (KD) on levels of tumor necrosis factor alpha (TNF-α, a classical pro-inflammatory cytokine), BDNF (brain-derived neurotrophic factor, commonly associated with synaptic plasticity), and S100B, an astrocyte neurotrophic cytokine involved in metabolism regulation.Main methodsYoung Wistar rats were fed during 8 weeks with control diet or two KD, containing different proportions of omega 6 and omega 3 polyunsaturated fatty acids. Contents of TNF-α, BDNF and S100B were measured by ELISA in two brain regions (hippocampus and striatum) as well as blood serum and cerebrospinal fluid.Key findingsOur data suggest that KD was able to reduce the levels of BDNF in the striatum (but not in hippocampus) and S100B in the cerebrospinal fluid of rats. These alterations were not affected by the proportion of polyunsaturated fatty acids offered. No changes in S100B content were observed in serum or analyzed brain regions. Basal TNF-α content was not affected by KD.SignificanceThese findings reinforce the importance of this diet as an inductor of alterations in the brain, and such changes might contribute to the understanding of the effects (and side effects) of KD in brain disorders.     

New Culicoides Latreille of the subgenus Mataemyia Vargas from Pará, Brazil (Diptera: Ceratopogonidae)

Two new species of Culicoides Latreille of the Neotropical subgenus Mataemyia Vargas are described and illustrated based on female specimens from Juruti, Pará, Brazil and compared with their similar congeners. This paper also presents a diagnosis of the subgenus Mataemyia and a systematic key for the identification of the 19 species of the subgenus.     

Use of sodC versus ctrA for real-time polymerase chain reaction-based detection of Neisseria meningitidis in sterile body fluids

We evaluated the use of a newly described sodC-based real-time-polymerase chain reaction (RT-PCR) assay for detecting Neisseria meningitidis in normally sterile sites, such as cerebrospinal fluid and serum. The sodC-based RT-PCR assay has an advantage over ctrA for detecting nongroupable N. meningitidis isolates, which are commonly present in asymptomatic pharyngeal carriage. However, in our study, sodC-based RT-PCR was 7.5% less sensitive than ctrA. Given the public health impact of possible false-negative results due to the use of the sodC target gene alone, sodC-based RT-PCR for the diagnosis of meningococcal meningitis should be used with caution.