Since, there is no direct synaptic connection between RIA and AVA, AVD or AVE interneurons, likely other neurons are also required to mediate signals from RIA to AVA, AVD and AVE. Our results suggest that the multi PDZ-domain protein MAGI-1 is required in RIA for the Axitinib integration of those environmental inputs during associative learning. On the other hand, memory consolidation, the retention of the conditioned behavior over time, requires the GLR-1 expressing interneurons AVA, AVD and likely AVE, where MAGI-1 is necessary to induce persisting changes in the synaptic GLR-1 cluster size. During associative conditioning, the size but not the number of GLR-1 clusters decrease, which might reflect an increased density of glutamate receptors at post-synaptic membranes. Recently, the long isoform of the C.elegans MAGI-1 was demonstrated to influence mechanosensory habituation and GLR1 receptor degradation through ubiquitination. However, it should also be noted that some, mostly PET studies have also reported opiate dependent activations in the ACC. Apart from the differences in stimulation and imaging technique, one reason for this discrepancy might be related to low spatial resolution in some studies, which would collapse signals from functionally distinct ACC subareas. This notion is supported by a recent study using considerably higher spatial resolution fMRI and showing opiate dependent activation and deactivation in neighboring ACC subregions during the same condition. In conclusion, our data reveals that the endogenous opioid system is affected by thermal stimuli in the absence of any specific cognitive manipulation. The hypothesis that endogenous opioids lead to a deactivation of the pregenual ACC is supported by our data showing that this effect can be blocked by the opioid receptor antagonist naloxone. During habituation the number of GLR-1 positive synapses decrease in the MAGI-1 mutant worms carrying a deletion in the long isoform, suggesting a decrease in glutamate signaling. This suggests that in H. virescens and in G. mellonella, like in S. frugiperda, X-tox proteins are not processed into individual bioactive defensins. Because the antimicrobial activity of insect plasma was found not to be associated to the presence of Spod-11-tox-derived defensins nor to the presence of larger Spod-11-tox processing products, we believe that overall, Spod-11-tox is not directly involved in the microorganism killing. In 1991, Sander and Schneider used Shannon entropy derived scores for positional conservation in alignment of proteins. To test this, we directly compared the relative sensitivity of diploid versus haploid deletion for genes that were identified in the diploid screen but not in the haploid screen. Concurrently, we screened for cross sensitivity to the S phase specific DNA damaging agents HU and MMS.