Widespread brain distribution of the Drosophila metabotropic glutamate receptor.

Glutamate is the predominant excitatory neurotransmitter in the vertebrate brain, whereas acetylcholine has been considered to play the same role in insects. Recent studies have, however, questioned the latter view by showing a rather general distribution of glutamate transporters. Here, we describe the expression pattern of the receptor DmGlu-A (DmGluRA), the unique homolog of vertebrate metabotropic glutamate receptors. Metabotropic glutamate receptors play important roles in the regulation of glutamatergic neurotransmission. Using a specific antibody, we report DmGluRA expression in most neuropile areas in both larvae and adults, but not in the lobes of the mushroom bodies. These observations suggest a key role for glutamate in the insect brain

Honey Bee Allatostatins Target Galanin/Somatostatin-Like Receptors and Modulate Learning: A Conserved Function?

International audienceSequencing of the honeybee genome revealed many neuropeptides and putative neuropeptide receptors, yet functional characterization of these peptidic systems is scarce. In this study, we focus on allatostatins, which were first identified as inhibitors of juvenile hormone synthesis, but whose role in the adult honey bee (Apis mellifera) brain remains to be determined. We characterize the bee allatostatin system, represented by two families: allatostatin A (Apime-ASTA) and its receptor (Apime-ASTA-R); and C-type allatostatins (Apime-ASTC and Apime-ASTCC) and their common receptor (Apime-ASTC-R). Apime-ASTA-R and Apime-ASTC-R are the receptors in bees most closely related to vertebrate galanin and somatostatin receptors, respectively. We examine the functional properties of the two honeybee receptors and show that they are transcriptionally expressed in the adult brain, including in brain centers known to be important for learning and memory processes. Thus we investigated the effects of exogenously applied allatostatins on appetitive olfactory learning in the bee. Our results show that allatostatins modulate learning in this insect, and provide important insights into the evolution of somatostatin/allatostatin signaling

Direct transport vs secondary transfer to level I trauma centers in a French exclusive trauma system: Impact on mortality and determinants of triage on road-traffic victims.

BackgroundTransporting a severely injured patient directly to a trauma center (TC) is consensually considered optimal. Nevertheless, disagreement persists regarding the association between secondary transfer status and outcome. The aim of the study was to compare adjusted mortality between road traffic trauma patients directly or secondarily transported to a level 1 trauma center (TC) in an exclusive French trauma system with a physician staffed prehospital emergency medical system (EMS).MethodsA retrospective cohort study was performed using 2015-2017 data from a regional trauma registry (Traumabase®), an administrative database on road-traffic accidents and prehospital-EMS records. Multivariate logistic regression models were computed to determine the role of the modality of admission on mortality and to identify factors associated with secondary transfer. The primary outcome was day-30 mortality. Results: During the study period, 121.955 victims of road-traffic accident were recorded among which 4412 trauma patients were admitted in the level 1 regional TCs, 4031 directly and 381 secondarily transferred from lower levels facilities. No significant association between all-cause 30-day mortality and the type of transport was observed (Odds ratio 0.80, 95% confidence interval (CI) [0.3-1.9]) when adjusted for potential confounders. Patients secondarily transferred were older, with low-energy mechanism and presented higher head and abdominal injury scores. Among all 947 death, 43 (4.5%) occurred in lower-level facilities. The population-based undertriage leading to death was 0.15%, 95%CI [0.12-0.19].ConclusionIn an exclusive trauma system with physician staffed prehospital care, road-traffic victims secondarily transferred to a TC do not have an increased mortality when compared to directly transported patients

Improvement in adherence to Capecitabine and Lapatinib by way of a therapeutic education program

International audienceA patient non-adherence with oral anticancer agents is a well-recognized barrier to effective treatment. The aim of this prospective study was to evaluate the efficacy of a therapeutic education program among non-adherent patients treated with Capecitabine alone or associated with Lapatinib

Aminoacid sequence alignment of Apime-ASTC-R and its <i>Drosophila</i> and human homologs.

<p>Sequence alignments of the predicted allatostatin C receptor in the honey bee <i>Apis mellifera</i> (<i>Apime-ASTC-R</i>, GenBank: XP_006560939.1) and of its homologs in the fruitfly <i>Drosophila melanogaster</i> (<i>Drostar1</i>, GenBank: NP_649040.2 and <i>Drostar2</i>, GenBank: NP_649039.4), and human (SSTR2, NP_001041.1). The amino acid position is indicated on the left. Conserved residues are in red, and conservative changes in blue. Grey bars indicate putative trans-membrane regions (TM1–TM7). Amino acids that are characteristic of class A GPCRs are indicated by *, open diamonds (◊) indicate putative N-linked glycolysation sites, # indicate cysteine residues for disulfide bridge (between TM2—TM3 and TM4 –TM5) or palmitoylation (intracellular domain), and dots (●) indicate conserved putative phosphorylation sites for PKA/C. Sequences are based on transcripts (cDNA).</p

Phylogenetic tree of <i>A</i>. <i>mellifera</i> and <i>D</i>. <i>melanogaster</i> allatostatin receptors with respect to their closest mouse homologs.

<p><i>Drosophila</i> gene names are indicated. For <i>M</i>. <i>musculus</i> receptors, abbreviations are: GALR (Galanin receptor), KISS1R (kisspeptin receptor), OPR (opioid receptor), MCHR (melanin concentrating hormone receptor), NPBWR (Neuropeptide B and W receptor), SSTR (somatostatin receptor). The bottom bar indicates the phylogenetic distance scale. The bootstrap values are displayed in red.</p

Apime-ASTA-R and Apime-ASTC-R display constitutive inhibitory activity, down-regulating cAMP.

<p>HEK cells transfected with Apime-ASTA-R or Apime-ASTC-R show lower levels of bioluminescence than mock-transfected cells (A). Bars represents mean+/-SD values of 8 transfections in duplicates (mock) or triplicates (Apime-AST-R). Forskolin analog NKH-477 has a reduced ability to increase bioluminescence levels in Apime-ASTA-R and Apime-ASTC-R transfected cells than in mock-transfected cells (B). Bars represent mean +/- SD values of 2 transfections in duplicates or triplicates. Application of increasing doses of Apime-ASTA on Apime-ASTA-R transfected cells induced a dose-dependent increase in bioluminescence (C). Application of increasing doses of Apime-ASTC on Apime-ASTC-R transfected cells did not change bioluminescence levels (D). Application of increasing doses of Apime-ASTCC on Apime-ASTC-R transfected cells increased bioluminescence levels at high concentrations (E). HEK cells transfected with luciferase reporter gene and an empty vector (mock-transfected) show a dose-dependent response to Apime-ASTCC (F). Bars represent mean +/- SD values of 3 transfections in triplicates.</p

Aminoacid sequence alignment of Apime-ASTA-R and its <i>Drosophila</i> and human homologs.

<p>Sequence alignments of the predicted allatostatin A receptor in the honey bee <i>Apis mellifera</i> (Apime-ASTA-R, GenBank: XP_006560262.1) and of its homologs in the fruit fly <i>Drosophila melanogaster</i> (DAR1, GenBank: NP_726877.2 and <i>DAR2</i>, GenBank: NP_524544.1) and human (GALR1, NP_001471.2). The amino acid position is indicated on the left. Conserved residues are in red, and conservative changes in blue. Vertical bars (|) indicate locations of putative introns; grey bars indicate putative trans-membrane regions (TM1–TM7). Amino acids that are characteristic of class A GPCRs are indicated by *, open diamonds (◊) indicate putative N-linked glycolysation sites, # indicate cysteine residues for disulfide bridge (between TM2—TM3 and TM4 –TM5) or palmitoylation (intracellular domain), and dots (●) indicate conserved putative phosphorylation sites for PKA/C. Sequences are based on transcripts (cDNA).</p

Dose-dependent learning impairment induced by allatostatins.

<p>Percentages of forager bees displaying conditioned proboscis extension responses (PER) in the third and last trial of conditioning, in honeybees injected with either vehicle alone (control bees, CT) or a given concentration of allatostatin A (A), C (B), or CC (C). For easier comparisons, <b>l</b>earning performances of control bees are set at 100% and those of all other groups are relative to CT. N = 120–182 (A), N = 70–80 (B) N = 56–87 (C). Significant decreases of learning performance, as compared to those of saline-injected bees, are indicated (*: p<0.05, **:p<0.01, ***:p<0.001).</p

Binding of radiolabelled Apime-ASTA <i>in vivo</i> and <i>in vitro</i>.

<p>¹²⁵I-Apime-ASTA binding to bee brain crude membranes was displaced by increasing concentrations of non-labeled Apime-ASTA (A). Competitive binding with Apime-ASTA and increasing concentrations of a somatostatin homolog (SOM230) (B). Bars represent mean+/-SD (n = 3). Curves were obtained by fitting the data using nonlinear regression analysis in the GraphPad Prism software.</p