Antagonistic effects of floral scent in an insect–plant interaction

In southwestern USA, the jimsonweed Datura wrightii and the nocturnal moth Manduca sexta form a pollinator–plant and herbivore–plant association. Because the floral scent is probably important in mediating this interaction, we investigated the floral volatiles that might attract M. sexta for feeding and oviposition. We found that flower volatiles increase oviposition and include small amounts of both enantiomers of linalool, a common component of the scent of hawkmoth-pollinated flowers. Because (+)-linalool is processed in a female-specific glomerulus in the primary olfactory centre of M. sexta, we hypothesized that the enantiomers of linalool differentially modulate feeding and oviposition. Using a synthetic mixture that mimics the D. wrightii floral scent, we found that the presence of linalool was not necessary to evoke feeding and that mixtures containing (+)- and/or (−)-linalool were equally effective in mediating this behaviour. By contrast, females oviposited more on plants emitting (+)-linalool (alone or in mixtures) over control plants, while plants emitting (−)-linalool (alone or in mixtures) were less preferred than control plants. Together with our previous investigations, these results show that linalool has differential effects in feeding and oviposition through two neural pathways: one that is sexually isomorphic and non-enantioselective, and another that is female-specific and enantioselective.     

Aberrant Amyloid Precursor Protein (APP) Processing in Hereditary Forms of Alzheimer Disease Caused by APP Familial Alzheimer Disease Mutations Can Be Rescued by Mutations in the APP GxxxG Motif

The identification of hereditary familial Alzheimer disease (FAD) mutations in the amyloid precursor protein (APP) and presenilin-1 (PS1) corroborated the causative role of amyloid-β peptides with 42 amino acid residues (Aβ42) in the pathogenesis of AD. Although most FAD mutations are known to increase Aβ42 levels, mutations within the APP GxxxG motif are known to lower Aβ42 levels by attenuating transmembrane sequence dimerization. Here, we show that aberrant Aβ42 levels of FAD mutations can be rescued by GxxxG mutations. The combination of the APP-GxxxG mutation G33A with APP-FAD mutations yielded a constant 60% decrease of Aβ42 levels and a concomitant 3-fold increase of Aβ38 levels compared with the Gly³³ wild-type as determined by ELISA. In the presence of PS1-FAD mutations, the effects of G33A were attenuated, apparently attributable to a different mechanism of PS1-FAD mutants compared with APP-FAD mutants. Our results contribute to a general understanding of the mechanism how APP is processed by the γ-secretase module and strongly emphasize the potential of the GxxxG motif in the prevention of sporadic AD as well as FAD.     

Sperm chemotaxis in marine invertebrates--molecules and mechanisms

Sperm are attracted by chemical substances which are released by the egg. This process is called chemotaxis. Several molecules that are involved in chemotactic signaling of sperm from marine invertebrates are described and a model of the signaling pathway is presented. We discuss the motor response during chemotaxis and propose a model of the navigation strategy of sperm.     

Motif inference reveals optimal CTL epitopes presented by HLA class I alleles highly prevalent in southern Africa

HIV-specific CTL play a central role in immune control of HIV. The basis for understanding the success or failure of this immune response requires identification of the specific epitopes targeted by CTL. However, in populations most severely affected by the global epidemic, this fundamental knowledge is hindered by the lack of characterization of many of the HLA class I alleles highly prevalent in such populations. Overall, the peptide-binding motif has been determined for a small minority (9%) of HLA class I alleles, with a strong bias toward those alleles prevalent in Caucasoid populations. These studies therefore set out to define, in a South African Zulu/Xhosa population at the epicenter of the epidemic, the epitopes presented by alleles highly prevalent, but for which the peptide-binding motif had not been characterized. Using a method of motif inference, epitopes presented by four such alleles prevalent in the Zulu/Xhosa population of Durban, South Africa, namely, B*3910, B*4201, B*8101, and Cw*1801, are described. Importantly, this approach may additionally facilitate optimization of epitopes in certain instances where conflicting reports in the literature exist regarding the peptide-binding motif, such as for HLA-A*2902, also highly prevalent in southern African populations. These data indicate that the previously anomalous position of HLA-A*2902 among HLA-A alleles, outside any recognized HLA-A supertype, is artifactual, and the true position of the A*2902 motif overlaps those of the A1 and A24 supertypes.     

Neuroanatomy of the sucking pump of the moth, Manduca sexta (Sphingidae, Lepidoptera)

Knowledge of the neuroanatomy of the sucking pump of Manduca sexta (Sphingidae) is valuable for studies of olfactory learning, pattern generators, and postembryonic modification of motor circuitry. The pump comprises a cibarial valve, a buccal pump, and an esophageal sphincter valve. Cibarial opener and closer muscles control the cibarial valve. Six pairs of dilator muscles and a compressor muscle operate the buccal pump. The cibarial opener and one pair of buccal dilator muscles are innervated by paired neurons in the tritocerebrum, and the cibarial opener has double, bilateral innervation. Their tritocerebral innervation indicates that these muscles evolved from labro-clypeal muscles. The remaining paired buccal dilator muscles each are innervated by an unpaired motor neuron in the frontal ganglion. These motor neurons project bilaterally through the frontal connectives to dendritic arborizations in the tritocerebrum. These projections also have a series of dendritic-like arborizations in the connectives. The cibarial closer and buccal compressor muscles are also innervated by motor neurons in the frontal ganglion, but only the closer muscle neuron projects bilaterally to the tritocerebrum. The innervation of the pump muscles indicates that they are associated with the stomodaeum, and, therefore, the buccal pump evolved from the anterior stomodaeum rather than from the cibarium.     

Dab1 tyrosine phosphorylation sites relay positional signals during mouse brain development

BACKGROUND: The extracellular protein Reln controls neuronal migrations in parts of the cortex, hippocampus and cerebellum. In vivo, absence of Reln correlates with up-regulation of the docking protein Dab1 and decreased Dab1 tyrosine phosphorylation. Loss of the Reln receptor proteins, apolipoprotein receptor 2 and very low density lipoprotein receptor, results in a Reln-like phenotype accompanied by increased Dab1 protein expression. Complete loss of Dab1, however, recapitulates the Reln phenotype. RESULTS: To determine whether Dab1 tyrosine phosphorylation affects Dab1 protein expression and positioning of embryonic neurons, we have identified Dab1 tyrosine phosphorylation sites. We then generated mice in which the Dab1 protein had all the potential tyrosine phosphorylation sites mutated. This mutant protein is not tyrosine phosphorylated during brain development and is not upregulated to the extent observed in the Reln or the apoER2 and VLDLR receptor mutants. Animals expressing the non-phosphorylated Dab1 protein have a phenotype similar to the dab1-null mutant. CONCLUSIONS: Dab1 is downregulated by the Reln signal in neurons in the absence of tyrosine phosphorylation. Dab1 tyrosine phosphorylation sites and not downregulation of Dab1 protein are required for Reln signaling.     

The behavioral context of common dolphin (Delphinus sp.) vocalizations

Correlations between surface behavior and concurrent underwater vocalizations were modeled for common dolphins (Delphinus spp.) in the Southern California Bight (SCB) over multiple field seasons. Clicks, pulsed calls, and whistles were examined, with a total of 50 call features identified. Call features were used to classify behavior using random forest decision trees, with rates of correct classification reaching 80.6% for fast travel, 84.6% for moderate travel, 59.8% for slow travel, and 58% for foraging behavior. Common dolphins spent most of their time traveling. The highest number of clicks, pulsed calls, and complex whistles were produced during fast travel. In contrast, during foraging there were few pulsed calls and whistles produced, and the whistles were simple with narrow bandwidths and few harmonics. Behavior and vocalization patterns suggest nocturnal foraging in offshore waters as the primary feeding strategy. Group size and spacing were strongly correlated with behavior and rates of calling, with higher call rates in dispersed traveling groups and lower call rates in loosely aggregated foraging groups. These results demonstrate that surface behavior can be classified using vocalization data, which builds the framework for behavioral studies of common dolphins using passive acoustic monitoring techniques.     

Comparative study of vascular prostheses coated with polycyclodextrins for controlled ciprofloxacin release

A textile polyester vascular graft was modified with cyclodextrins to obtain a new implant capable of releasing antibiotics (here ciprofloxacin, CFX) over prolonged time periods and thereby reducing the risk of post-operative infections. In this study, we compared samples modified with native and modified cyclodextrins, presenting different cavity sizes (β or γ cyclodextrins) and different substituent groups (hydroxypropyl and methyl). Drug release was measured in water, phosphate buffer pH 7.4 and blood plasma. The inclusion of CFX in the cyclodextrins cavities was observed in solution by two-dimensional (1)H NMR spectroscopy and confirmed by (1)F NMR measurements. Grafts modification with all cyclodextrins induced an increase of their sorption capacity towards CFX whose extent depended on the nature of the cyclodextrin: a 4-fold and 10-fold increase was observed in the cases of hydroxypropyl cyclodextrins and methylated β-cyclodextrin, respectively. Depending on the type of release medium and nature of CD, different CFX release kinetics were obtained. The discussion highlighted not only the role of the host guest complexation, but also that of the electrostatic interactions that occur between the anionic crosslinks of the cyclodextrins polymers, and CFX that presents a zwitterionic character. The microbiological assessment confirmed sustained CFX release in human plasma and demonstrated antibacterial efficiency of CD modified prostheses against Staphylococcus aureus and Escherichia coli for at least 24h (compared to 4h in the case of virgin grafts).     

Regulation of Toll-like receptor 4-mediated immune responses through Pasteurella multocida toxin-induced G protein signalling

Background

Lipopolysaccharide (LPS)-triggered Toll-like receptor (TLR) 4-signalling belongs to the key innate defence mechanisms upon infection with Gram-negative bacteria and triggers the subsequent activation of adaptive immunity. There is an active crosstalk between TLR4-mediated and other signalling cascades to secure an effective immune response, but also to prevent excessive inflammation. Many pathogens induce signalling cascades via secreted factors that interfere with TLR signalling to modify and presumably escape the host response. In this context heterotrimeric G proteins and their coupled receptors have been recognized as major cellular targets. Toxigenic strains of Gram-negative Pasteurella multocida produce a toxin (PMT) that constitutively activates the heterotrimeric G proteins G??_q, G??₁₃ and G??_i independently of G protein-coupled receptors through deamidation. PMT is known to induce signalling events involved in cell proliferation, cell survival and cytoskeleton rearrangement.

Results

Here we show that the activation of heterotrimeric G proteins through PMT suppresses LPS-stimulated IL-12p40 production and eventually impairs the T cell-activating ability of LPS-treated monocytes. This inhibition of TLR4-induced IL-12p40 expression is mediated by G??_i-triggered signalling as well as by G?|?-dependent activation of PI3kinase and JNK. Taken together we propose the following model: LPS stimulates TLR4-mediated activation of the NF?B-pathway and thereby the production of TNF-??, IL-6 and IL-12p40. PMT inhibits the production of IL-12p40 by G??_i-mediated inhibition of adenylate cyclase and cAMP accumulation and by G?|?-mediated activation of PI3kinase and JNK activation.

Conclusions

On the basis of the experiments with PMT this study gives an example of a pathogen-induced interaction between G protein-mediated and TLR4-triggered signalling and illustrates how a bacterial toxin is able to interfere with the host??s immune response.