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1.
Nat Neurosci ; 27(7): 1318-1332, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38769153

RESUMEN

Emotion recognition and the resulting responses are important for survival and social functioning. However, how socially derived information is processed for reliable emotion recognition is incompletely understood. Here, we reveal an evolutionarily conserved long-range inhibitory/excitatory brain network mediating these socio-cognitive processes. Anatomical tracing in mice revealed the existence of a subpopulation of somatostatin (SOM) GABAergic neurons projecting from the medial prefrontal cortex (mPFC) to the retrosplenial cortex (RSC). Through optogenetic manipulations and Ca2+ imaging fiber photometry in mice and functional imaging in humans, we demonstrate the specific participation of these long-range SOM projections from the mPFC to the RSC, and an excitatory feedback loop from the RSC to the mPFC, in emotion recognition. Notably, we show that mPFC-to-RSC SOM projections are dysfunctional in mouse models relevant to psychiatric vulnerability and can be targeted to rescue emotion recognition deficits in these mice. Our findings demonstrate a cortico-cortical circuit underlying emotion recognition.


Asunto(s)
Emociones , Corteza Prefrontal , Animales , Emociones/fisiología , Corteza Prefrontal/fisiología , Ratones , Masculino , Humanos , Neuronas GABAérgicas/fisiología , Vías Nerviosas/fisiología , Somatostatina/metabolismo , Reconocimiento en Psicología/fisiología , Ratones Endogámicos C57BL , Optogenética , Femenino , Giro del Cíngulo/fisiología
2.
Genes Brain Behav ; 21(5): e12787, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34889032

RESUMEN

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.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Esquizofrenia , Animales , Trastorno del Espectro Autista/genética , Trastorno Autístico/genética , Deleción Cromosómica , Cromosomas Humanos Par 16/genética , Variaciones en el Número de Copia de ADN , Humanos , Ratones , Esquizofrenia/genética , Conducta Social
3.
Proc Natl Acad Sci U S A ; 118(44)2021 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-34711679

RESUMEN

Empirical audit and review is an approach to assessing the evidentiary value of a research area. It involves identifying a topic and selecting a cross-section of studies for replication. We apply the method to research on the psychological consequences of scarcity. Starting with the papers citing a seminal publication in the field, we conducted replications of 20 studies that evaluate the role of scarcity priming in pain sensitivity, resource allocation, materialism, and many other domains. There was considerable variability in the replicability, with some strong successes and other undeniable failures. Empirical audit and review does not attempt to assign an overall replication rate for a heterogeneous field, but rather facilitates researchers seeking to incorporate strength of evidence as they refine theories and plan new investigations in the research area. This method allows for an integration of qualitative and quantitative approaches to review and enables the growth of a cumulative science.


Asunto(s)
Investigación Empírica , Reproducibilidad de los Resultados , Inseguridad Alimentaria , Humanos , Dimensión del Dolor , Proyectos de Investigación , Asignación de Recursos
5.
Artículo en Inglés | MEDLINE | ID: mdl-32432053

RESUMEN

The human immune cell response against bacterial biofilms is a crucial, but still poorly investigated area of research. Herein, we aim to establish an in vitro host cell-biofilm interaction model suitable to investigate the peripheral blood mononuclear cell (PBMC) response to Pseudomonas aeruginosa biofilms. P. aeruginosa biofilms were obtained by incubating bacteria in complete RPMI 1640 medium with 10% human plasma for 24 h. PBMC obtained from healthy donors were added to preformed P. aeruginosa biofilms. Following a further 24 h incubation, we assessed (i) PBMC viability and activation; (ii) cytokine profiles in the supernatants; and (iii) CFU counts of biofilm forming bacteria. Cell-death was <10% upon 24 h incubation of PBMC with P. aeruginosa biofilms. PBMC incubated for 24 h with preformed P. aeruginosa biofilms were significantly more activated compared to PBMC incubated alone. Interestingly, a marked activation of CD56+CD3- natural killer (NK) cells was observed that reached 60% of NK cells as an average of different donors. In the culture supernatants of PBMC co-cultured with P. aeruginosa biofilms, not only pro-inflammatory (IL-1ß, IFN-γ, IL-6, and TNF-α) but also anti-inflammatory (IL-10) cytokines were significantly increased as compared to PBMC incubated alone. Furthermore, incubation of biofilms with PBMC, caused a statistically significant increase in the CFU number of P. aeruginosa, as compared to biofilms incubated without PBMC. In order to assess whether PBMC products could stimulate the growth of P. aeruginosa biofilms, we incubated preformed P. aeruginosa biofilms with or without supernatants obtained from the co-cultures of PBMC with biofilms. In the presence of the supernatants, the CFU count of biofilm-derived P. aeruginosa, was two to seven times higher than those of biofilms incubated without supernatants (P < 0.01). Overall, the results obtained shed light on the reciprocal interaction between human PBMC and P. aeruginosa biofilms. P. aeruginosa biofilms induced PBMC activation and cytokine secretion but, in turn, the presence of PBMC and/or PBMC-derived components enhanced the number of P. aeruginosa biofilm associated bacteria. This may indicate a successful bacterial defensive/persistence strategy against immune response.


Asunto(s)
Biopelículas , Leucocitos Mononucleares/microbiología , Pseudomonas aeruginosa , Citocinas , Humanos
6.
Int J Mol Sci ; 20(24)2019 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-31847119

RESUMEN

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.


Asunto(s)
Antibacterianos , Adhesión Bacteriana/efectos de los fármacos , Biopelículas/efectos de los fármacos , Quitosano , Materiales Biocompatibles Revestidos , Pseudomonas aeruginosa/fisiología , Staphylococcus epidermidis/fisiología , Titanio , Antibacterianos/química , Antibacterianos/farmacología , Biopelículas/crecimiento & desarrollo , Quitosano/química , Quitosano/farmacología , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Titanio/química , Titanio/farmacología
7.
J Med Chem ; 46(12): 2325-33, 2003 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-12773037

RESUMEN

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.


Asunto(s)
Factor 1 de Crecimiento de Fibroblastos/química , Factores de Crecimiento de Fibroblastos/síntesis química , Mitógenos/síntesis química , Oligopéptidos/síntesis química , Fragmentos de Péptidos/síntesis química , Péptidos Cíclicos/síntesis química , Células 3T3 , Animales , Dicroismo Circular , Factores de Crecimiento de Fibroblastos/química , Factores de Crecimiento de Fibroblastos/farmacología , Humanos , Espectroscopía de Resonancia Magnética , Ratones , Mitógenos/química , Mitógenos/farmacología , Modelos Moleculares , Oligopéptidos/química , Oligopéptidos/farmacología , Fragmentos de Péptidos/química , Fragmentos de Péptidos/farmacología , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacología , Conformación Proteica , Timidina/metabolismo
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