Psychological aspects of pre-adolescents or adolescents with precocious puberty: A systematic review

Precocious puberty (PP) is an illness that appears when puberty, begins some years earlier than usual, provoking inferences in preadolescents and adolescents and their families. Therefore, the aim is to analyze if psychological consequences can be observed in groups of preadolescents or adolescents with PP. Method: A bibliographic search of the scientific literature was made following the PRISMA guide in the following databases: ProQuest, Psychinfo, Web Of Science, and Scopus. 592 studies were found, were uploaded to Covidence to make a screening, of which finally 6 were included for the revision according to the inclusion and exclusion criteria. Two independent evaluators made the search, selection, data extraction and quality evaluation of studies independently. The agreement degree between both was excellent in all of the cases. Results: 211 preadolescents participated in total in all studies, of which 99 were preadolescents with PP, with a mean age of 8,94 years old. Studies evaluated so heterogeneous variables, such as psychopathology, selfimage, neuropsychological and cognitive variables, and reasons to delay or stop PP. The quality of studies was moderated especially due to the low quality of the studies design, which were mostly transversal, and the representativity of the sample, being selected by convenience. Conclusions and implications: More research is needed to evaluate the psychological consequences of the PP diagnosis in pediatrics, and its protection factors, because none of the studies approached this question. We consider that it is necessary to increment the quality of these studies, and that these take a biopsychosocial perspective

Does Variation of the Inter-Domain Linker Sequence Modulate the Metal Binding Behaviour of Helix pomatia Cd-Metallothionein?

Snail metallothioneins (MTs) constitute an ideal model to study structure/function relationships in these metal-binding polypeptides. Helix pomatia harbours three MT isoforms: the highly specific CdMT and CuMT, and an unspecific Cd/CuMT, which represent paralogous proteins with extremely different metal binding preferences while sharing high sequence similarity. Preceding work allowed assessing that, although, the Cys residues are responsible for metal ion coordination, metal specificity or preference is achieved by diversification of the amino acids interspersed between them. The metal-specific MT polypeptides fold into unique, energetically-optimized complexes of defined metal content, when binding their cognate metalions, while they produce a mixture of complexes, none of them representing a clear energy minimum, with non-cognate metal ions. Another critical, and so far mostly unexplored, region is the stretch linking the individual MT domains, each of which represents an independent metal cluster. In this work, we have designed and analyzed two HpCdMT constructs with substituted linker segments, and determined their coordination behavior when exposed to both cognate and non-cognate metal ions. Results unequivocally show that neither length nor composition of the inter-domain linker alter the features of the Zn(II)- and Cd(II)-complexes, but surprisingly that they influence their ability to bind Cu(I), the non-cognate metal ion

Hints for Metal-Preference Protein Sequence Determinants: Different Metal Binding Features of the Five Tetrahymena thermophila Metallothioneins

The metal binding preference of metallothioneins (MTs) groups them in two extreme subsets, the Zn/Cd- and the Cu-thioneins. Ciliates harbor the largest MT gene/protein family reported so far, in-cluding 5 paralogs that exhibit relatively low sequence similarity, excepting MTT2 and MTT4. In Tet-rahymena thermophila, three MTs (MTT1, MTT3 and MTT5) were considered Cd-thioneins and two (MTT2 and MTT4) Cu-thioneins, according to gene expression inducibility and phylogenetic analysis. In this study, the metal-binding abilities of the five MTT proteins were characterized, to obtain information about the folding and stability of their cognate- and non-cognate metal complexes, and to characterize the T. thermophila MT system at protein level. Hence, the five MTTs were recombinantly synthesized as Zn2+-, Cd2+- or Cu+-complexes, which were analyzed by electrospray mass spectrometry (ESI-MS), circular dichroism (CD), and UV-vis spectrophotometry. Among the Cd-thioneins, MTT1 and MTT5 were optimal for Cd2+ coordination, yielding unique Cd17- and Cd8- complexes, respectively. When binding Zn2+, they rendered a mixture of Zn-species. Only MTT5 was capable to coordinate Cu+, although yielding heteronuclear Zn-, Cu-species or highly unstable Cu-homometallic species. MTT3 exhibited poor binding abilities both for Cd2+ and for Cu+, and although not optimally, it yielded the best result when coordinating Zn2+. The two Cu-thioneins, MTT2 and MTT4 isoforms formed homometallic Cu-complexes (major Cu20-MTT) upon synthesis in Cu-supplemented hosts. Contrarily, they were unable to fold into stable Cd-complexes, while Zn-MTT species were only recovered for MTT4 (major Zn10-MTT4). Thus, the metal binding preferences of the five T. thermophila MTs correlate well with their previous classification as Cd- and Cu-thioneins, and globally, they can be classified from Zn/Cd- to Cu-thioneins according to the gradation: MTT1>MTT5>MTT3>MTT4>MTT2. The main mechanisms underlying the evolution and specialization of the MTT metal binding preferences may have been in-ternal tandem duplications, presence of doublet and triplet Cys patterns in Zn/Cd-thioneins, and op-timization of site specific amino acid determinants (Lys for Zn/Cd- and Asn for Cu-coordination)

The fungus Tremella mesenterica encodes the longest metallothionein currently known: gene, protein and metal binding characterization

Fungal Cu-thioneins, and among them, the paradigmatic Neurospora crassa metallothio- nein (MT) (26 residues), were once considered as the shortest MTs -the ubiquitous, versa- tile metal-binding proteins- among all organisms, and thus representatives of their primeval forms. Nowadays, fungal MTs of diverse lengths and sequence features are known, follow- ing the huge heterogeneity of the Kingdom of Fungi. At the opposite end of N . crassa MT, the recently reported Cryptococcus neoformans CnMT1 and CnMT2 (122 and 186 aa) con- stitute the longest reported fungal MTs, having been identified as virulence factors of this pathogen. CnMTs are high-capacity Cu-thioneins that appear to be built by tandem amplifi- cation of a basic unit, a 7-Cys segment homologous to N . crassa MT. Here, we report the in silico , in vivo and in vitro study of a still longer fungal MT, belonging to Tremella mesenter- ica (TmMT), a saprophytic ascomycete. The TmMT gene has 10 exons, and it yields a 779-bp mature transcript that encodes a 257 residue-long protein. This MT is also built by repeated fragments, but of variable number of Cys: six units of the 7-Cys building blocks- CXCX 3 CSCPPGXCXCAXCP-, two fragments of six Cys, plus three Cys at the N-terminus. TmMT metal binding abilities have been analyzed through the spectrophotometric and spectrometric characterization of its recombinant Zn-, Cd- and Cu-complexes. Results allow it to be unambiguous classified as a Cu-thionein, also of extraordinary coordinating capacity. According to this feature, when the TmMT cDNA is expressed in MT-devoid yeast cells, it is capable of restoring a high Cu tolerance level. Since it is not obvious that T . mesenterica shares the same physiological needs for a high capacity Cu-binding protein with C . neoformans , the existence of this peculiar MT might be better explained on the basis of a possible role in Cu-handling for the Cu-enzymes responsible in lignin degradation pathways

Psychoeducational intervention in psychology students on suicide through a lecture and the implementation of an emotional kit

[EN] Suicide is a global health problem that has been aggravated by the COVID-19 pandemic. Despite its great psychosocial relevance, there are a large number of myths about suicide. The aim of the study was to raise awareness of basic aspects of suicide through attractive teaching methodologies that combine the virtual and face-to-face environments and that allow the theoretical and practical knowledge necessary to assess, intervene and prevent the suicide to be integrated in a cooperative manner. Ninety-two students from the Psychology Degree at the University of Valencia participated (M=21.04; SD=1.81). First, they completed a battery of questions about myths and realities of suicide; then, they received the training; and, finally, they completed the battery again. The results showed that students obtained a higher mean number of most psychologically accepted responses answers in the identification of myths and realities after the training (t=-5.87, p<.001). The presence of myths related to suicide among university students is evident. It is also concluded that the theoretical-practical training presented in this study could be a useful tool to enhance the acquisition of knowledge and skills in students about suicide assessment, prevention and intervention.[ES] El suicidio consituye un problema de salud mundial que ha sido agravado por la pandemia de COVID-19. A pesar de su gran relevancia psicosocial, existe un elevado número de mitos acerca del suicidio. El objetivo del estudio fue dar a conocer aspectos básicos sobre el suicidio a través de metodologías docentes atractivas que combinan el entorno virtual con el presencial y que permiten integrar de forma cooperativa los conocimientos teórico-prácticos necesarios para evaluar, intervenir y prevenir el suicidio. Participaron 92 estudiantes del Grado de Psicología de la Universitat de València (M=21,04; DT=1,81). Primero, completaron una batería de preguntas acerca de mitos y realidades del suicidio; a continuación, recibieron la formación; y, finalmente, completaron la batería de nuevo. Los resultados mostraron que el alumnado obtuvo una media de respuestas psicológicamente más aceptadas más elevada en la identificación de mitos y realidades tras la formación (t=-5,87; p&lt;,001). Se evidencia la presencia de mitos relacionados con el suicidio entre el estudiantado universitario. Asimismo, se concluye que la formación teórico-práctica presentada en este estudio podría ser una herramienta útil para potenciar la adquisión de conocimientos y competencias en el alumnado acerca de la evaluación, la prevención y la intervención en el suicidio.Lacomba-Trejo, L.; Valero-Moreno, S.; De La Barrera, U.; Schoeps, K.; Mónaco, E.; Tamarit, A.; Rodríguez, E.... (2022). Intervención psicoeducativa en estudiantes de psicología sobre el suicidio mediante una conferencia y la realización de un botiquín emocional. Editorial Universitat Politècnica de València. 707-717. https://doi.org/10.4995/INRED2022.2022.1592570771

New insights in the study and characterization of fungal metallothioneins and their relationship with the pathogenic activity

Las metalotioneínas (MTs) constituyen una superfamilia de metaloproteínas de bajo peso molecular caracterizada por un contenido extraordinario de cisteína, que les proporciona la capacidad de coordinar iones de metales pesados ​​a través de los correspondientes enlaces metal-tiolato. Estas proteínas son polimórficas en un gran número de organismos estudiados hasta ahora, además de que se han encontrado grandes similitudes entre MTs de diferentes organismos. Estas observaciones sugieren que una diversificación de las MTs se ha producido como consecuencia de sucesivos eventos de duplicación de genes en o entre diferentes taxones. En cada caso, la actividad que la MT necesita realizar en el organismo puede haber producido su evolución para servir a diferentes funciones relacionadas con el metal molecular, tales como la homeostasis esencial iones metálicos (Zn2+ o Cu+), la defensa frente a iones metálicos tóxicos (como Cd2+, Pb2+ o Hg2+), el barrido de radicales libres y especies de oxígeno reactivo (ROS), y una amplia gama de tensiones celulares. Por lo tanto, las MTs en un organismo dado muestran preferencias por la coordinación específica de iones metálicos y también para formar complejos con un número concreto de iones metálicos unidos, independientemente del grado de su similitud a nivel de secuencia de proteínas. Por esta razón, el presente trabajo de tesis doctoral se ha basado primero en clasificar un gran número de MTs, pertenecientes a organismos de hongos, en cuatro familias, según su longitud de secuencia de aminoácidos. Una vez clasificadas las MTs, un estudio de las similitudes entre sus secuencias de aminoácidos ha sido plausible, y también una comparación entre sus capacidades de coordinación proteína/metal y la especificidad por diferentes iones metálicos. Con el fin de dilucidar estas capacidades mencionadas, la biosíntesis de las MTs en diferentes entornos de contenido metálico ha sido necesaria. La biosíntesis y el plegamiento de las MTs sobre sus iones metálicos afines dan como resultado la formación de complejos energéticamente optimizados. Sin embargo, cuando la síntesis tiene lugar sobre iones metálicos no afines, normalmente se produce una mezcla de especies, reflejando la cantidad de iones metálicos disponibles en su entorno molecular o, por el contrario, la síntesis puede no ser exitosa. Con el estudio de todas estas propiedades, los intentos de aclarar las funciones de las MTs en cada organismo son posibles. En este trabajo de tesis doctoral, se han estudiado MTs de organismos fúngicos, la mayoría patógenos, por la importancia de descubrir el papel de las MTs en el proceso de virulencia y patogenicidad. Los avances en estos hallazgos pueden ayudar a la humanidad a nivel biológico y médico.Metallothioneins (MTs) constitute a superfamily of metalloproteins with low molecular weight characterized by an extraordinary cysteine content, which provides them the ability to coordinate heavy-metal ions through the corresponding metal-thiolate bonds. These proteins are polymorphic in a huge number of organisms studied up to now, besides great similarities have been found between MTs from different organisms. These observations suggest that a diversification of MTs have been produced as a consequence of successive gene duplication events in or between different taxa. In each case, the activity that the MT needs to accomplish in the organism may have produced the evolution to serve different molecular metal-related functions, such as essential metal ion homeostasis (Zn2+ or Cu+), the defence in front of toxic metal ions (i.e. Cd2+, Pb2+ or Hg2+), the scavenging of free radicals and reactive oxygen species (ROS), and a wide range of cell stresses. Therefore, MTs in a given organism exhibit preferences for specific metal ion coordination and also to form complexes with a concrete number of metal ions bonded, independently of the degree of their similarity at protein sequence level. For this reason, the present PhD thesis work has been based first on classify a huge number of MTs, belonging to fungi organisms, in four families, according to their amino acid sequence length. Once classified the MTs, a study of the similarities between their amino acid sequences have been plausible, and also a comparison between their protein/metal coordination abilities and specificity for different metal ions. In order to elucidate these last-mentioned capabilities, the biosynthesis of the MTs in different metal content environments has been necessary. MTs biosynthesis and folding about their cognate metal ions result in the formation of energetically optimized complexes. But, when the synthesis takes place about non-cognate metal ions, normally a mixture of species is produced, by reflecting the amount of metal ions available in its molecular environment, or by contrast the synthesis may not be successful. With the study of all these properties, attempts to clarify the functions of MTs in each organism are possible. In this PhD thesis work, MTs from fungi organisms, most of them pathogenic, have been studied, due to the importance to discover the role of the MTs in the process of virulence and pathogenicity. Advances in these findings may help the humanity at biological and medical level

New insights in the study and characterization of fungal metallothioneins and their relationship with the pathogenic activity /

Las metalotioneínas (MTs) constituyen una superfamilia de metaloproteínas de bajo peso molecular caracterizada por un contenido extraordinario de cisteína, que les proporciona la capacidad de coordinar iones de metales pesados ​​a través de los correspondientes enlaces metal-tiolato. Estas proteínas son polimórficas en un gran número de organismos estudiados hasta ahora, además de que se han encontrado grandes similitudes entre MTs de diferentes organismos. Estas observaciones sugieren que una diversificación de las MTs se ha producido como consecuencia de sucesivos eventos de duplicación de genes en o entre diferentes taxones. En cada caso, la actividad que la MT necesita realizar en el organismo puede haber producido su evolución para servir a diferentes funciones relacionadas con el metal molecular, tales como la homeostasis esencial iones metálicos (Zn2+ o Cu+), la defensa frente a iones metálicos tóxicos (como Cd2+, Pb2+ o Hg2+), el barrido de radicales libres y especies de oxígeno reactivo (ROS), y una amplia gama de tensiones celulares. Por lo tanto, las MTs en un organismo dado muestran preferencias por la coordinación específica de iones metálicos y también para formar complejos con un número concreto de iones metálicos unidos, independientemente del grado de su similitud a nivel de secuencia de proteínas. Por esta razón, el presente trabajo de tesis doctoral se ha basado primero en clasificar un gran número de MTs, pertenecientes a organismos de hongos, en cuatro familias, según su longitud de secuencia de aminoácidos. Una vez clasificadas las MTs, un estudio de las similitudes entre sus secuencias de aminoácidos ha sido plausible, y también una comparación entre sus capacidades de coordinación proteína/metal y la especificidad por diferentes iones metálicos. Con el fin de dilucidar estas capacidades mencionadas, la biosíntesis de las MTs en diferentes entornos de contenido metálico ha sido necesaria. La biosíntesis y el plegamiento de las MTs sobre sus iones metálicos afines dan como resultado la formación de complejos energéticamente optimizados. Sin embargo, cuando la síntesis tiene lugar sobre iones metálicos no afines, normalmente se produce una mezcla de especies, reflejando la cantidad de iones metálicos disponibles en su entorno molecular o, por el contrario, la síntesis puede no ser exitosa. Con el estudio de todas estas propiedades, los intentos de aclarar las funciones de las MTs en cada organismo son posibles. En este trabajo de tesis doctoral, se han estudiado MTs de organismos fúngicos, la mayoría patógenos, por la importancia de descubrir el papel de las MTs en el proceso de virulencia y patogenicidad. Los avances en estos hallazgos pueden ayudar a la humanidad a nivel biológico y médico.Metallothioneins (MTs) constitute a superfamily of metalloproteins with low molecular weight characterized by an extraordinary cysteine content, which provides them the ability to coordinate heavy-metal ions through the corresponding metal-thiolate bonds. These proteins are polymorphic in a huge number of organisms studied up to now, besides great similarities have been found between MTs from different organisms. These observations suggest that a diversification of MTs have been produced as a consequence of successive gene duplication events in or between different taxa. In each case, the activity that the MT needs to accomplish in the organism may have produced the evolution to serve different molecular metal-related functions, such as essential metal ion homeostasis (Zn2+ or Cu+), the defence in front of toxic metal ions (i.e. Cd2+, Pb2+ or Hg2+), the scavenging of free radicals and reactive oxygen species (ROS), and a wide range of cell stresses. Therefore, MTs in a given organism exhibit preferences for specific metal ion coordination and also to form complexes with a concrete number of metal ions bonded, independently of the degree of their similarity at protein sequence level. For this reason, the present PhD thesis work has been based first on classify a huge number of MTs, belonging to fungi organisms, in four families, according to their amino acid sequence length. Once classified the MTs, a study of the similarities between their amino acid sequences have been plausible, and also a comparison between their protein/metal coordination abilities and specificity for different metal ions. In order to elucidate these last-mentioned capabilities, the biosynthesis of the MTs in different metal content environments has been necessary. MTs biosynthesis and folding about their cognate metal ions result in the formation of energetically optimized complexes. But, when the synthesis takes place about non-cognate metal ions, normally a mixture of species is produced, by reflecting the amount of metal ions available in its molecular environment, or by contrast the synthesis may not be successful. With the study of all these properties, attempts to clarify the functions of MTs in each organism are possible. In this PhD thesis work, MTs from fungi organisms, most of them pathogenic, have been studied, due to the importance to discover the role of the MTs in the process of virulence and pathogenicity. Advances in these findings may help the humanity at biological and medical level

Does Variation of the Inter-Domain Linker Sequence Modulate the Metal Binding Behaviour of Helix pomatia Cd-Metallothionein?

Snail metallothioneins (MTs) constitute an ideal model to study structure/function relationships in these metal-binding polypeptides. Helix pomatia harbours three MT isoforms: the highly specific CdMT and CuMT, and an unspecific Cd/CuMT, which represent paralogous proteins with extremely different metal binding preferences while sharing high sequence similarity. Preceding work allowed assessing that, although, the Cys residues are responsible for metal ion coordination, metal specificity or preference is achieved by diversification of the amino acids interspersed between them. The metal-specific MT polypeptides fold into unique, energetically-optimized complexes of defined metal content, when binding their cognate metal ions, while they produce a mixture of complexes, none of them representing a clear energy minimum, with non-cognate metal ions. Another critical, and so far mostly unexplored, region is the stretch linking the individual MT domains, each of which represents an independent metal cluster. In this work, we have designed and analyzed two HpCdMT constructs with substituted linker segments, and determined their coordination behavior when exposed to both cognate and non-cognate metal ions. Results unequivocally show that neither length nor composition of the inter-domain linker alter the features of the Zn(II)- and Cd(II)-complexes, but surprisingly that they influence their ability to bind Cu(I), the non-cognate metal ion

Does Variation of the Inter-Domain Linker Sequence Modulate the Metal Binding Behaviour of Helix pomatia Cd-Metallothionein?

Snail metallothioneins (MTs) constitute an ideal model to study structure/function relationships in these metal-binding polypeptides. Helix pomatia harbours three MT isoforms: the highly specific CdMT and CuMT, and an unspecific Cd/CuMT, which represent paralogous proteins with extremely different metal binding preferences while sharing high sequence similarity. Preceding work allowed assessing that, although, the Cys residues are responsible for metal ion coordination, metal specificity or preference is achieved by diversification of the amino acids interspersed between them. The metal-specific MT polypeptides fold into unique, energetically-optimized complexes of defined metal content, when binding their cognate metal ions, while they produce a mixture of complexes, none of them representing a clear energy minimum, with non-cognate metal ions. Another critical, and so far mostly unexplored, region is the stretch linking the individual MT domains, each of which represents an independent metal cluster. In this work, we have designed and analyzed two HpCdMT constructs with substituted linker segments, and determined their coordination behavior when exposed to both cognate and non-cognate metal ions. Results unequivocally show that neither length nor composition of the inter-domain linker alter the features of the Zn(II)- and Cd(II)-complexes, but surprisingly that they influence their ability to bind Cu(I), the non-cognate metal ion

Hints for Metal-Preference Protein Sequence Determinants: Different Metal Binding Features of the Five Tetrahymena thermophila Metallothioneins

The metal binding preference of metallothioneins (MTs) groups them in two extreme subsets, the Zn/Cd - and the Cu - thioneins. Ciliates harbor the largest MT gene/protein family reported so far, i n- cluding 5 paralogs that exhibit relatively low sequence similarity, excepting MTT2 and MTT4. I n Te t- rahymena thermophila , three MTs (MTT1, MTT3 and MTT5) were considered Cd - thioneins and two (MTT2 and MTT4) Cu - thioneins, according to gene expression inducibility and phylogenetic analysis. In this study, the metal - binding abilities of the five MTT pr oteins were characterized, to obtain information about the folding and stability of their cognate - and non - cognate metal complexes, and to characterize the T. thermophila MT system at protein level. Hence, the five MTTs were recombinantly synthesized as Zn 2+ - , Cd 2+ - or Cu + - complexes, which were analyzed by electrospray mass spectrometry (ESI - MS), circular dichroism (CD), and UV - vis spectrophotometry. Among the Cd - thioneins, MTT1 and MTT5 were optimal for Cd 2+ coordination, yielding unique Cd 17 - and Cd 8 - com plexes, respectively. When binding Zn 2+ , they rendered a mixture of Zn - species. Only MTT5 was capable to coordinate Cu + , although yielding heteronuclear Zn - , Cu - species or highly unstable Cu - homometallic species. MTT3 exhibited poor binding abilities both for Cd 2+ and for Cu + , and although not optimally, it yielded the best result when coordinating Zn 2+ . The two Cu - thioneins, MTT2 and MTT4 isoforms formed homometallic Cu - complexes (major Cu 20 - MTT) upon synthesis in Cu - supplemented hosts. Contrarily, they we re unable to fold into stable Cd - complexes, while Zn - MTT species were only recovered for MTT4 (major Zn 10 - MTT4). Thus, the metal binding preferences of the five T. thermophila MTs correlate well with their previous classification as Cd - and Cu - thioneins, a nd globally, they can be classified from Zn/Cd - to Cu - thioneins according to the gradation: MTT1>MTT5>MTT3>MTT4>MTT2. The main mechanisms underlying the evolution and specialization of the MTT metal binding preferences may have been i n- ternal tandem duplica tions, presence of doublet and triplet Cys patterns in Zn/Cd - thioneins, and o p- timization of site specific amino acid determinants (Lys for Zn/Cd - and Asn for Cu - coordination)