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The pathological process of prion diseases implicates that the normal physiological cellular prion protein (PrPC) converts into misfolded abnormal scrapie prion (PrPSc) through post-translational modifications that increase β-sheet conformation. We recently demonstrated that HuPrP(90–231) thermal unfolding is partially irreversible and characterized by an intermediate state (β-PrPI), which has been revealed to be involved in the initial stages of PrPC fibrillation, with a seeding activity comparable to that of human infectious prions. In this study, we report the thermal unfolding characterization, in cell-mimicking conditions, of the truncated (HuPrP(90–231)) and full-length (HuPrP(23–231)) human prion protein by means of CD and NMR spectroscopy, revealing that HuPrP(90–231) thermal unfolding is characterized by two successive transitions, as in buffer solution. The amyloidogenic propensity of HuPrP(90–231) under crowded conditions has also been investigated. Our findings show that although the prion intermediate, structurally very similar to β-PrPI, forms at a lower temperature compared to when it is dissolved in buffer solution, in cell-mimicking conditions, the formation of prion fibrils requires a longer incubation time, outlining how molecular crowding influences both the equilibrium states of PrP and its kinetic pathways of folding and aggregation. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate whether empathizing and systemizing are part of the parental broad autism phenotype (BAP). Parents (N = 76) of preschool children with a diagnosis of ASD and parents (N = 48) of typically developing (TD) children completed the Empathy Quotient (EQ) and Systemizing Quotient-Revised (SQ-R) questionnaires. The E-S discrepancy (D score) was used to test for sex differences in five "brain types". Our results suggest that the E-S theory do not seem to be part of the BAP. However, a stronger drive to systemize than empathize (Type S brain) could be a highly inheritable cognitive endophenotype of mothers of children with ASD. This study should be repeated with a larger sample size.

Background: In the present study we investigated whether peptides derived from the entire SARS-CoV-2 proteome share homology to TAAs (tumor-associated antigens) and cross-reactive CD8+ T cell can be elicited by the BNT162b2 preventive vaccine or the SARS-CoV-2 natural infection. Methods and results: Viral epitopes with high affinity (<100nM) to the HLAA* 02:01 allele were predicted. Shared and variant-specific epitopes were identified. Significant homologies in amino acidic sequence have been found between SARS-CoV-2 peptides and multiple TAAs, mainly associated with breast, liver, melanoma and colon cancers. The molecular mimicry of the viral epitopes and the TAAs was found in all viral proteins, mostly the Orf 1ab and the Spike, which is included in the BNT162b2 vaccine. Predicted structural similarities confirmed the sequence homology and comparable patterns of contact with both HLA and TCR α and β chains were observed. CD8+ T cell clones cross-reactive with the paired peptides have been found by MHC class l-dextramer staining. Conclusions: Our results show for the first time that several SARS-COV-2 antigens are highly homologous to TAAs and cross-reactive T cells are identified in infected and BNT162b2 preventive vaccinated individuals. The implication would be that the SARS-Cov-2 pandemic could represent a natural preventive immunization for breast, liver, melanoma and colon cancers. In the coming years, real-world evidences will provide the final proof for such immunological experimental evidence. Moreover, such SARS-CoV-2 epitopes can be used to develop "multicancer" off-the-shelf preventive/therapeutic vaccine formulations, with higher antigenicity and immunogenicity than over-expressed tumor self-antigens, for the potential valuable benefit of thousands of cancer patients around the World. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate whether empathizing and systemizing are part of the parental broad autism phenotype (BAP). Parents (N = 76) of preschool children with a diagnosis of ASD and parents (N = 48) of typically developing (TD) children completed the Empathy Quotient (EQ) and Systemizing Quotient-Revised (SQ-R) questionnaires. The E-S discrepancy (D score) was used to test for sex differences in five 'brain types'. Our results suggest that the E-S theory do not seem to be part of the BAP. However, a stronger drive to systemize than empathize (Type S brain) could be a highly inheritable cognitive endophenotype of mothers of children with ASD. This study should be repeated with a larger sample size., Author(s): Francesco Craig [sup.1] , Andrea De Giacomo [sup.2] , Rosa Savino [sup.1] , Marta Ruggiero [sup.1] , Luigi Russo [sup.1] , Isabella Fanizza [sup.1] , Lucia Margari [sup.2] , [...]

Background: The Picture Exchange Communication System (PECS) is a common treatment choice for non-verbal children with autism. However, little empirical evidence is available on the usefulness of PECS in treating social-communication impairments in autism. Aims: To test the effects of PECS on social-communicative skills in children with autism, concurrently taking into account standardized psychometric data, standardized functional assessment of adaptive behaviour, and information on social-communicative variables coded in an unstructured setting. Methods & Procedures: Eighteen preschool children (mean age = 38.78 months) were assigned to two intervention approaches, i.e. PECS and Conventional Language Therapy (CLT). Both PECS (Phases I-IV) and CLT were delivered three times per week, in 30-min sessions, for 6 months. Outcome measures were the following: Autism Diagnostic Observation Schedule (ADOS) domain scores for Communication and Reciprocal Social Interaction; Language and Personal-Social subscales of the Griffiths' Mental Developmental Scales (GMDS); Communication and Social Abilities domains of the Vineland Adaptive Behavior Scales (VABS); and several social-communicative variables coded in an unstructured setting. Outcomes & Results: Results demonstrated that the two groups did not differ at Time 1 (pre-treatment assessment), whereas at Time 2 (post-test) the PECS group showed a significant improvement with respect to the CLT group on the VABS social domain score and on almost all the social-communicative abilities coded in the unstructured setting (i.e. joint attention, request, initiation, cooperative play, but not eye contact). Conclusions & Implications: These findings showed that PECS intervention (Phases I-IV) can improve social-communicative skills in children with autism. This improvement is especially evident in standardized measures of adaptive behaviour and measures derived from the observation of children in an unstructured setting. (Contains 5 tables.)

A twin study is an excellent means of assessing the contribution of heritability to motor behaviour. We present a movement video-analysis of a monozygotic twins pair with a motor repertoire which is almost totally constituted by persistent and subcontinuous motor stereotypies. Purpose: The specific aim of this study is to verify the heritable quantum of motor behaviour and to determine which among the motor patterns we analysed are more likely to be conditioned by inheritance. Methods: Stereotyped movements were videotaped in two standardized sessions: at rest and in relation to preordained sensory stimulations. We estimated the concordance index (CI) between the observers to evaluate the reliability of the observations. The validity was accepted as being CI greater than 0.80. Results: The results showed a very high concordance rate (greater than 90%) for all the stereotypies analysed. An almost superimposable trend of the stereotyped movements was found both at rest and in relation to the sensory stimulations. Conclusions: Such strong data suggest that genetic factors have a primary influence on all the movement disorders analysed. This study contributes to a better understanding of the complex relationships between genes and functions. (Contains 1 table and 3 figures.)

Persistence and degradation are important factors in determining the safe use of such synthetic products, and numerous studies have been addressed to develop pesticide remediation methods aimed at ameliorating these features. In this frame, the use of different cyclodextrins (CDs) molecules has attracted considerable attention due to their well-known non-toxic nature, limited environmental impact, and capability to reduce the environmental and health risks of pesticides. CDs appear to be a valuable tool for the elimination of pesticides from polluted areas as well as for better pesticide formulations that positively influence their hydrolysis or degradation. The present work investigates the interaction between β-cyclodextrins and three commonly used pesticides (i.e., chlorpropham, monuron, and propanil) both in solution and in the solid state by means of UV-Vis, FT-IR, and X-ray powder diffractometry. We show that such interactions result in all three cases in the formation of inclusion complexes with a 1:1 stoichiometry and binding constants (Kb) of 369.9 M−1 for chlorpropham, 292.3 M−1 for monuron, and 298.3 M−1 for propanil. We also report the energy-minimized structures in silico for each complex. Our data expand and complement the available literature data in indicating CDs as a low-cost and very effective tool capable of modulating the properties that determine the environmental fate of pesticides. [ABSTRACT FROM AUTHOR]

The crucial role of integrin in pathological processes such as tumor progression and metastasis formation has inspired intense efforts to design novel pharmaceutical agents modulating integrin functions in order to provide new tools for potential therapies. In the past decade, we have investigated the biological proprieties of the chimeric peptide RGDechi, containing a cyclic RGD motif linked to an echistatin C-terminal fragment, able to specifically recognize αvβ3 without cross reacting with αvβ5 and αIIbβ3 integrin. Additionally, we have demonstrated using two RGDechi-derived peptides, called RGDechi1-14 and ψRGDechi, that chemical modifications introduced in the C-terminal part of the peptide alter or abolish the binding to the αvβ3 integrin. Here, to shed light on the structural and dynamical determinants involved in the integrin recognition mechanism, we investigate the effects of the chemical modifications by exploring the conformational space sampled by RGDechi1-14 and ψRGDechi using an integrated natural-abundance NMR/MD approach. Our data demonstrate that the flexibility of the RGD-containing cycle is driven by the echistatin C-terminal region of the RGDechi peptide through a coupling mechanism between the N- and C-terminal regions. [ABSTRACT FROM AUTHOR]

A strict interplay is known to involve copper and zinc in many cellular processes. For this reason, the results of copper's interaction with zinc binding proteins are of great interest. For instance, copper interferences with the DNA-binding activity of zinc finger proteins are associated with the development of a variety of diseases. The biological impact of copper depends on the chemical properties of its two common oxidation states (Cu(I) and Cu(II)). In this framework, following the attention addressed to unveil the effect of metal ion replacement in zinc fingers and in zinc-containing proteins, we explore the effects of the Zn(II) to Cu(I) or Cu(II) replacement in the prokaryotic zinc finger domain. The prokaryotic zinc finger protein Ros, involved in the horizontal transfer of genes from A. tumefaciens to a host plant infected by it, belongs to a family of proteins, namely Ros/MucR, whose members have been recognized in different bacteria symbionts and pathogens of mammals and plants. Interestingly, the amino acids of the coordination sphere are poorly conserved in most of these proteins, although their sequence identity can be very high. In fact, some members of this family of proteins do not bind zinc or any other metal, but assume a 3D structure similar to that of Ros with the residues replacing the zinc ligands, forming a network of hydrogen bonds and hydrophobic interactions that surrogates the Zn-coordinating role. These peculiar features of the Ros ZF domain prompted us to study the metal ion replacement with ions that have different electronic configuration and ionic radius. The protein was intensely studied as a perfectly suited model of a metal-binding protein to study the effects of the metal ion replacement; it appeared to tolerate the Zn to Cd substitution, but not the replacement of the wildtype metal by Ni(II), Pb(II) and Hg(II). The structural characterization reported here gives a high-resolution description of the interaction of copper with Ros, demonstrating that copper, in both oxidation states, binds the protein, but the replacement does not give rise to a functional domain. [ABSTRACT FROM AUTHOR]