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Genetic 16p11.2 and 22q11.2 deletions and duplications in humans may alter behavioral developmental trajectories increasing the risk of autism and schizophrenia spectrum disorders, and of attention-deficit/hyperactivity disorder. In this review, we will concentrate on 16p11.2 and 22q11.2 deletions' effects on social functioning, beyond diagnostic categorization. We highlight diagnostic and social sub-constructs discrepancies. Notably, we contrast evidence from human studies with social profiling performed in several mouse models mimicking 16p11.2 and 22q11.2 deletion syndromes. Given the complexity of social behavior, there is a need to assess distinct social processes. This will be important to better understand the biology underlying such genetic-dependent dysfunctions, as well as to give perspective on how therapeutic strategies can be improved. Bridges and divergent points between human and mouse studies are highlighted. Overall, we give challenges and future perspectives to sort the genetics of social heterogeneity.

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In the era of antimicrobial resistance, the identification of new antimicrobials is a research priority at the global level. In this regard, the attention towards functional antimicrobial polymers, with biomedical/pharmaceutical grade, and exerting anti-infective properties has recently grown. The aim of this study was to evaluate the antibacterial, antibiofilm, and antiadhesive properties of a number of quaternized chitosan derivatives that have displayed significant muco-adhesive properties and wound healing promotion features in previous studies. Low (QAL) and high (QAH) molecular weight quaternized chitosan derivatives were synthetized and further modified with thiol moieties or pendant cyclodextrin, and their antibacterial activity evaluated as minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC). The ability of the derivatives to prevent biofilm formation was assessed by crystal violet staining. Both QAL and QAH derivatives exerted a bactericidal and/or inhibitory activity on the growth of P. aeruginosa and S. epidermidis. The same compounds also showed marked dose-dependent anti-biofilm activity. Furthermore, the high molecular weight derivative (QAH) was used to functionalize titanium plates. The successful functionalization, demonstrated by electron microscopy, was able to partially inhibit the adhesion of S. epidermidis at 6 h of incubation. The shown ability of the chitosan derivatives tested to both inhibit bacterial growth and/or biofilm formation of clinically relevant bacterial species reveals their potential as multifunctional molecules against bacterial infections.

Fibroblast growth factors (FGFs) are regulatory proteins associated with a number of physiological and pathological states. On the basis of data suggesting a functional role for specific regions of human acidic FGF (aFGF), a linear peptide encompassing residues 99-108 (peptide1) and its cyclic analogue (peptide 2) were synthesized and their functional and structural features were investigated. While peptide 1 is inactive on Balb/c 3T3 fibroblasts, peptide 2 is mitogenic with ED(50) of approximately 50 microM. Moreover, peptide 1 is not able to inhibit the binding of human aFGF to cellular receptors whereas peptide 2 exhibits significant inhibitory activity. The NMR-derived solution conformers indicated the presence, only in peptide 2, of structural elements that we believe are related to its ability to emulate the biological activity of the native protein. These results suggest that the expression of mitogenic activity in short peptides, besides the presence of specific amino acids, requires the existence of stable structural features. In addition, they indicate that the introduction of chemical restraints in peptides can provide novel possibilities for the development of receptor agonists or antagonists.

Duranti, M. A., Franzoni, L., Sartor, G., Benedetti, A., Iwai, L. K., Gruber, A., Zingales, B., Guzman, F., Kalil, J., Spisni, A., and Cunha-Neto, E. 1999. Trypanosoma cruzi: Conformational preferences of antigenic peptides bearing the immunodominant epitope of the B13 antigen. Experimental Parasitology 93 , 38–44. The Trypanosoma cruzi recombinant protein B13 contains tandemly repeated domains and shows high sensitivity in the serological diagnosis of Chagas' disease. It has been shown that the immunodominant epitope of B13 is contained in the GDKPSLFGQAAAGDKPSLF- NH 2 sequence and that the hexapeptide AAAGDK seems to be the “core” of that epitope. Three peptides containing that “core” sequence, one corresponding to the entire repeat motif GDKPSLFGQ AAAGDK PSLF- NH 2 , pB13, and two smaller fragments, FGQ AAAGDK - NH 2 , S4, and Q AAAGDK PS- NH 2 , S5, have been tested in competitive ELISA with recombinant protein B13 in the solid phase against 40 chagasic sera from Brazilian patients. The median percentage inhibition for pB13, S4, and S5 were, respectively, 91, 86, and 68%. The possibility that the distinct antigenic activity of those peptides correlates with the existence of preferential conformational properties has been investigated by CD and NMR spectroscopy. Results indicate their propensity to adopt a helical configuration, centered in the AAAGDK sequence, and whose extent and stability directly correlates with the peptides' antigenicity. The data are discussed in the light of the existence of conformational preferences involving immunodominant epitopes in tandemly repeated antigens.