Multiplexing of motor information in the discharge of a collision detecting neuron during escape behaviors

Locusts possess an identified neuron, the descending contralateral movement detector (DCMD), conveying visual information about impending collision from the brain to thoracic motor centers. We built a telemetry system to simultaneously record, in freely behaving animals, the activity of the DCMD and of motoneurons involved in jump execution. Cocontraction of antagonistic leg muscles, a required preparatory phase, was triggered after the DCMD firing rate crossed a threshold. Thereafter, the number of DCMD spikes predicted precisely motoneuron activity and jump occurrence. Additionally, the time of DCMD peak firing rate predicted that of jump. Ablation experiments suggest that the DCMD, together with a nearly identical ipsilateral descending neuron, is responsible for the timely execution of the escape. Thus, three distinct features that are multiplexed in a single neuron's sensory response to impending collision-firing rate threshold, peak firing time, and spike count-probably control three distinct motor aspects of escape behaviors.     

Synthesis, structure-affinity relationships, and molecular modeling studies of novel pyrazolo[3,4-c]quinoline derivatives as adenosine receptor antagonists

This paper reports the study of new 2-phenyl- and 2-methylpyrazolo[3,4-c]quinolin-4-ones (series A) and 4-amines (series B), designed as adenosine receptor (AR) antagonists. The synthesized compounds bear at the 6-position various groups, with different lipophilicity and steric hindrance, that were thought to increase human A(1) and A(2A) AR affinities and selectivities, with respect to those of the parent 6-unsubstituted compounds. In series A, this modification was not tolerated since it reduced AR affinity, while in series B it shifted the binding towards the hA(1) subtype. To rationalize the observed structure-affinity relationships, molecular docking studies at A(2A)AR-based homology models of the A(1) and A(3) ARs and at the A(2A)AR crystal structure were carried out.     

Investigation of multiple susceptibility loci for inflammatory bowel disease in an Italian cohort of patients

Background

Recent GWAs and meta-analyses have outlined about 100 susceptibility genes/loci for inflammatory bowel diseases (IBD). In this study we aimed to investigate the influence of SNPs tagging the genes/loci PTGER4, TNFSF15, NKX2-3, ZNF365, IFNG, PTPN2, PSMG1, and HLA in a large pediatric- and adult-onset IBD Italian cohort.

Methods

Eight SNPs were assessed in 1,070 Crohn''s disease (CD), 1,213 ulcerative colitis (UC), 557 of whom being diagnosed at the age of ≤16 years, and 789 healthy controls. Correlations with sub-phenotypes and major variants of NOD2 gene were investigated.

Results

The SNPs tagging the TNFSF15, NKX2-3, ZNF365, and PTPN2 genes were associated with CD (P values ranging from 0.037 to 7×10⁻⁶). The SNPs tagging the PTGER4, NKX2-3, ZNF365, IFNG, PSMG1, and HLA area were associated with UC (P values 0.047 to 4×10⁻⁵). In the pediatric cohort the associations of TNFSF15, NKX2-3 with CD, and PTGER4, NKX2-3, ZNF365, IFNG, PSMG1 with UC, were confirmed. Association with TNFSF15 and pediatric UC was also reported. A correlation with NKX2-3 and need for surgery (P  =  0.038), and with HLA and steroid-responsiveness (P  =  0.024) in UC patients was observed. Moreover, significant association in our CD cohort with TNFSF15 SNP and colonic involvement (P  =  0.021), and with ZNF365 and ileal location (P  =  0.024) was demonstrated.

Conclusions

We confirmed in a large Italian cohort the associations with CD and UC of newly identified genes, both in adult and pediatric cohort of patients, with some influence on sub-phenotypes.     

Secondary metabolite profile in induced tetraploids of wild Solanum commersonii Dun

The main aim of this work was to study the leaf secondary metabolite profiles of artificially induced tetraploids (2n=4x=48) of Solanum commersonii, a diploid (2n=2x=24) wild potato species. The tetraploid genotypes of S. commersonii were produced by oryzalin treatment. Both HPLC-UV and LC/MS analyses revealed that there were no qualitative differences in the metabolite profiles between the diploid S. commersonii and its tetraploids. By contrast, the results showed that the phenylpropanoid content was generally significantly higher in the tetraploids than in the diploid S. commersonii. Concerning the glycoalkaloids (GAs), the results provided evidence that the content of minor GAs (solanidenediol triose, solanidadienol lycotetraose, and solanidenol lycotetraose) was higher in tetraploids than in the diploid progenitor, while the content of major GAs (dehydrodemissine and dehydrocommersonine) was significantly higher in diploid S. commersonii than in its tetraploid genotypes. The results are discussed from the practical perspective of potato biodiversity enhancement.     

Humoral response to the Anopheles gambiae salivary protein gSG6: a serological indicator of exposure to Afrotropical malaria vectors

Salivary proteins injected by blood feeding arthropods into their hosts evoke a saliva-specific humoral response which can be useful to evaluate exposure to bites of disease vectors. However, saliva of hematophagous arthropods is a complex cocktail of bioactive factors and its use in immunoassays can be misleading because of potential cross-reactivity to other antigens. Toward the development of a serological marker of exposure to Afrotropical malaria vectors we expressed the Anopheles gambiae gSG6, a small anopheline-specific salivary protein, and we measured the anti-gSG6 IgG response in individuals from a malaria hyperendemic area of Burkina Faso, West Africa. The gSG6 protein was immunogenic and anti-gSG6 IgG levels and/or prevalence increased in exposed individuals during the malaria transmission/rainy season. Moreover, this response dropped during the intervening low transmission/dry season, suggesting it is sensitive enough to detect variation in vector density. Members of the Fulani ethnic group showed higher anti-gSG6 IgG response as compared to Mossi, a result consistent with the stronger immune reactivity reported in this group. Remarkably, anti-gSG6 IgG levels among responders were high in children and gradually declined with age. This unusual pattern, opposite to the one observed with Plasmodium antigens, is compatible with a progressive desensitization to mosquito saliva and may be linked to the continued exposure to bites of anopheline mosquitoes. Overall, the humoral anti-gSG6 IgG response appears a reliable serological indicator of exposure to bites of the main African malaria vectors (An. gambiae, Anopheles arabiensis and, possibly, Anopheles funestus) and it may be exploited for malaria epidemiological studies, development of risk maps and evaluation of anti-vector measures. In addition, the gSG6 protein may represent a powerful model system to get a deeper understanding of molecular and cellular mechanisms underlying the immune tolerance and progressive desensitization to insect salivary allergens.     

Genetic patchiness in European eel adults evidenced by molecular genetics and population dynamics modelling

Disentangling the demographic processes that determine the genetic structure of a given species is a fundamental question in conservation and management. In the present study, the population structure of the European eel was examined with a multidisciplinary approach combining the fields of molecular genetics and population dynamics modelling. First, we analyzed a total of 346 adult specimens of known age collected in three separate sample sites using a large panel of 22 EST-linked microsatellite loci. Second, we developed a European eel-specific model to unravel the demographic mechanisms that can produce the level of genetic differentiation estimated by molecular markers. This is the first study that reveals a pattern of genetic patchiness in maturing adults of the European eel. A highly significant genetic differentiation was observed among samples that did not follow an Isolation-by-Distance or Isolation-by-Time pattern. The observation of genetic patchiness in adults is likely to result from a limited parental contribution to each spawning event as suggested by our modelling approach. The value of genetic differentiation found is predicted by the model when reproduction occurs in a limited number of spawning events isolated from each other in time or space, with an average of 130-375 breeders in each spawning event. Unpredictability in spawning success may have important consequences for the life-history evolution of the European eel, including a bet-hedging strategy (distributing reproductive efforts over time) which could in turn guarantee successful reproduction of some adults.