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Resumo Neste artigo apresentamos uma pesquisa de mestrado cujo objetivo principal foi conhecer o que crianças pensam sobre o que é família e quais critérios utilizam para defini-la. O campo da pesquisa, construído através das pistas do Método Cartográfico, consistiu em 6 entrevistas em grupo, totalizando 22 crianças entre 6 e 11 anos, moradoras da cidade do Rio de Janeiro. As entrevistas incluíram a produção de desenhos de família, recurso utilizado como disparador da discussão. Percebemos que as crianças entrevistadas experimentam flexibilidade para conjugar aspectos que consideram importantes no entendimento dos laços familiares, como afeto, convivência e relações sanguíneas, que se entremeiam, se sobrepõem, se movimentam, nos remetendo ao conceito deleuziano de dobra. Ao focalizarmos o modo como elas entrelaçam seus critérios, concluímos que nos oferecem um olhar amplo sobre as famílias, aberto à multiplicidade, dando maior importância à qualidade afetiva dos relacionamentos. Abstract This paper presents the results of a master’s thesis on what children think a family is and what criteria they use to define it. Inspired by the Cartographic Method, the research consisted of 6 group interviews, totaling 22 children between 6 and 11 years old, living in the city of Rio de Janeiro, Brazil. Discussion was triggered by the production of family drawings. The children interviewed showed different ways of combining aspects considered important to understand family ties, such as affection, interaction and blood relations, which intermingle, overlap, move, recalling Deleuze’s concept of fold. In conclusion, focusing on how children intertwine their criteria offers us a broad look at families, open to multiplicity, giving greater importance to the affective quality of relationships. Résumé Cet article présente les résultats d’une thèse de master sur ce que les enfants pensent être une famille et sur les critères qu’ils utilisent pour la définir. Inspirée par la Méthode Cartographique, la recherche a consisté en 6 entretiens de groupe, totalisant 22 enfants âgés de 6 à 11 ans, vivant dans la ville de Rio de Janeiro, au Brésil. La discussion a été déclenchée par la production de dessins de famille. Les enfants interrogés ont montré différentes manières de combiner des aspects considérés comme importants pour comprendre les liens familiaux, tels que l’affection, la coexistence et les relations de sang, qui s’entremêlent, se chevauchent, se déplacent, rappelant la concept deleuzien de flexion. Enfin, se concentrer sur la façon dont les enfants entrelacent leurs critères nous offrent un regard large sur les familles, ouvert à la multiplicité, donnant plus d’importance à la qualité affective des relations. Resumen En este artículo presentamos parte de la investigación de maestría cuyo objetivo fue conocer qué piensan los niños sobre lo que es la familia y qué criterios utilizan para definirla. El campo de investigación, construido a partir del método cartográfico, consistió en 6 entrevistas grupales, en total 22 niños entre los 6 y los 11 años, residentes en la ciudad de Río de Janeiro. Las entrevistas incluyeron la producción de dibujos familiares, un recurso utilizado para desencadenar la discusión. Los niños entrevistados tienen flexibilidad para combinar aspectos que consideran importantes en su comprensión de los lazos familiares, como el afecto, la convivencia y los lazos de sangre, que se entremezclan, se superponen, se mueven y aluden al concepto deleuziano de pliegue. Centrándonos en cómo entrelazan sus criterios, concluimos que los niños nos ofrecen una mirada amplia sobre las familias, abierta a la multiplicidad, y con mayor importancia a la calidad afectiva de las relaciones.

The human N-glycosylases SMUG1 and MBD4 catalyze the removal of uracil residues from DNA resulting from cytosine deamination or replication errors. For polymorphic variants of SMUG1 (G90C, P240H, N244S, N248Y) and the MBD4^(cat) catalytic domain (S470L, G507S, R512W, H557D), the structures of enzyme-substrate complexes were obtained by molecular dynamic simulation. It was experimentally found that the SNP variants of SMUG1, N244S and N248Y, had increased catalytic activity compared to the wild-type enzyme, probably due to the acceleration of the dissociation of the enzyme-product complex and an increase in the enzyme turnover rate. All other SNP variants of SMUG1 (G90C, P240H) and MBD4^(cat), in which amino acid substitutions disrupted the substrate binding region and/or active site, had significantly lower catalytic activity than the wild-type enzymes.

Human apurinic/apyrimidinic endonuclease APE1 catalyzes endonucleolytic hydrolysis of phosphodiester bonds on the 5' side of structurally unrelated damaged nucleotides in DNA or native nucleotides in RNA. APE1 additionally possesses 3'-5'-exonuclease, 3'-phosphodiesterase, and 3'-phosphatase activities. According to structural data, endo- and exonucleolytic cleavage of DNA is executed in different complexes when the excised residue is everted from the duplex or placed within the intrahelical DNA cavity without nucleotide flipping. In this study, we investigated the functions of residues Arg177, Arg181, Tyr171 and His309 in the APE1 endo- and exonucleolytic reactions. The interaction between residues Arg177 and Met270, which was hypothesized recently to be a switch for endo- and exonucleolytic catalytic mode regulation, was verified by pre-steady-state kinetic analysis of the R177A APE1 mutant. The function of another DNA-binding-site residue, Arg181, was analyzed too; it changed its conformation when enzyme-substrate and enzyme-product complexes were compared. Mutation R181A significantly facilitated the product dissociation stage and only weakly affected DNA-binding affinity. Moreover, R181A reduced the catalytic rate constant severalfold due to a loss of contact with a phosphate group. Finally, the protonation/deprotonation state of residues Tyr171 and His309 in the catalytic reaction was verified by their substitution. Mutations Y171F and H309A inhibited the chemical step of the AP endonucleolytic reaction by several orders of magnitude with retention of capacity for (2R,3S)-2-(hydroxymethyl)-3-hydroxytetrahydrofuran-containing-DNA binding and without changes in the pH dependence profile of AP endonuclease activity, indicating that deprotonation of these residues is likely not important for the catalytic reaction.

Mit einem Vorwort von Ludger M. Hermanns Joan Riviere, Grete Bibring, Fanny Lowtzky, Grete Obernik und Eva Rosenfeld waren Psychoanalytikerinnen der Generation nach Sigmund Freud. Geboren im ausgehenden 19. Jahrhundert durchlebten sie von radikalen Umbrüchen geprägte Jahre, und dennoch fand jede von ihnen ihren eigenen bemerkenswerten Weg. Nina Bakman beleuchtet ihr Leben und Arbeiten. Obernik und Lowtzky arbeiteten in Palästina/Israel vorwiegend mit Kindern in Not. Bibring war die erste Frau, die als Professorin für Medizin an der Harvard Medical School lehrte. Rosenfeld nahm sich schwer erziehbarer Mädchen an und gründete eine Schule mit psychoanalytisch geschultem Lehrpersonal. Riviere, die als Einzige nicht aus dem »Dritten Reich« fliehen musste, arbeitete als Übersetzerin an der ersten englischen Freud-Ausgabe. Sie alle wirkten unter schwierigen historischen Umständen für Kinder, für Patient*innen, für die Psychoanalyse. Jede dieser Frauen nahm auf ihre eigene Weise eine dienende Funktion ein – doch nicht alle bekamen die Anerkennung, die sie verdient hätten.

Resumo Neste artigo apresentamos uma pesquisa de mestrado cujo objetivo principal foi conhecer o que crianças pensam sobre o que é família e quais critérios utilizam para defini-la. O campo da pesquisa, construído através das pistas do Método Cartográfico, consistiu em 6 entrevistas em grupo, totalizando 22 crianças entre 6 e 11 anos, moradoras da cidade do Rio de Janeiro. As entrevistas incluíram a produção de desenhos de família, recurso utilizado como disparador da discussão. Percebemos que as crianças entrevistadas experimentam flexibilidade para conjugar aspectos que consideram importantes no entendimento dos laços familiares, como afeto, convivência e relações sanguíneas, que se entremeiam, se sobrepõem, se movimentam, nos remetendo ao conceito deleuziano de dobra. Ao focalizarmos o modo como elas entrelaçam seus critérios, concluímos que nos oferecem um olhar amplo sobre as famílias, aberto à multiplicidade, dando maior importância à qualidade afetiva dos relacionamentos.

In the repair of the damage to bases, human apurinic/apyrimidinic (AP) endonuclease 1 (APE1) is a key participant via the DNA base excision repair pathway. APE1 cleaves AP sites in DNA, which are potentially cytotoxic and highly mutagenic if left unrepaired. According to existing structural data, this enzyme’s active site contains many polar amino acid residues, which form extensive contacts with a DNA substrate. A few alternative catalytic mechanisms of the phosphodiester bond hydrolysis by APE1 have been reported. Here, the kinetics of conformational changes of the enzyme and of DNA substrate molecules were studied during the recognition and cleavage of the abasic site in the pH range from 5.5 to 9.0 using stopped-flow fluorescence techniques. The activity of APE1 increased with an increase in pH because of acceleration of the rates of catalytic complex formation and of the catalytic reaction. Molecular dynamics simulation uncovered a significant increase in the pKₐ of His-309 located in the active site of the enzyme. This finding revealed that the observed enhancement of enzymatic activity with pH could be associated with deprotonation of not only Tyr-171 but also His-309. The obtained data allowed us to hypothesize that the ionized state of these residues could be a molecular switch between the alternative catalytic mechanisms, which involve different functionalities of these residues throughout the reaction.

Grete Bibring (1899–1977) was a representative of the second generation of analysts. Having emigrated from Vienna to London in 1938, she left for Boston in 1941 where she made a remarkable career. In 1946, she became head of the department of psychiatry at the Beth Israel Hospital at Harvard and, from 1961, the first woman professor of medicine there. She maintained a connection with European psychoanalysis in the person of Anna Freud, with whom she corresponded regularly. Their letters contain an interesting exchange of ideas about psychoanalytic institutions (e.g. the American Psychoanalytical Association) and papers (e.g. on pregnancy). It is also the testimony of an exceptional friendship.

Giriş: Yalnızca vücut kitle indeksine dayalı olarak yapılan sağlıkla ilgili yaşam kalitesi çalışmaları, özellikle fazla kilolu bireylerde net sonuçlar vermemektedir. Vücut kitle indeksi ve bel çevresi ölçümlerinin birlikte değerlendirilmesi, bu alanda daha iyi fikir verebilir. Yöntem: SF-36 Yaşam Kalitesi Ölçeği 18 yaş ve üstü 398 kadına uygulandı. Katılımcılar vücut kitle indekslerine göre gruplandırıldı ve fazla kilolu bireyler ayrıca bel çevresi ölçümlerine göre gruplara ayrıldı. Her bir alt ölçeği karşılaştırmak için Kruskal-Wallis One- way ANOVA istatistiksel analizleri kullanılmıştır. Bulgular: Normal ağırlıktan sınıf III obeziteye kadar tüm fiziksel ve mental alt ölçeklerdeki skorlar fazla kilolu grup dışında düşme eğilimindeydi. Normal kilolu bireylerle karşılaştırıldığında, fazla kilolu katılımcıların mental alt ölçeklerindeki skorların arttığı ancak bunun diğer bulgulardan farklı olarak istatistiksel olarak anlamlı olmadığı saptandı. Fazla kilolu grup bel çevresi ölçümlerine göre ayrı ayrı incelendiğinde; risk grupları arasında istatistiksel olarak anlamlı farklılıklar tespit edildi. Mental skorların yüksek riskli grupta normal risk grubuna göre anlamlı olarak azaldığı görüldü. (p, Introduction: Health-related quality of life studies performed only based on body mass index does not provide clear results, especially in overweight individuals. The evaluation of body mass index and waist circumference measurements together can offer better insights in this area. Methods: The SF-36 Quality of Life Scale was applied to 398 women aged 18 years and over. The participants were grouped according to body mass index, and the overweight individuals were further divided into groups based on waist circumference measurements. To compare each sub-scale, the Kruskal-Wallis 1 - way ANOVA statistics were used. Results: From the normal weight to class III obesity, the scores in all physical and mental subscales tended to decline, except in the overweight group. Compared to the individuals with normal weight, the overweight participants’ scores in the mental subscales were increased but this was not statistically significant, unlike the other findings. We examined the overweight group separately according to the waist circumference measurements and detected statistically significant differences between the risk groups. The mental scores were significantly decreased in the high-risk group compared to the normal risk group (p

The human N-glycosylases SMUG1 and MBD4 catalyze the removal of uracil residues from DNA resulting from cytosine deamination or replication errors. For polymorphic variants of SMUG1 (G90C, P240H, N244S, N248Y) and the MBD4^(cat) catalytic domain (S470L, G507S, R512W, H557D), the structures of enzyme-substrate complexes were obtained by molecular dynamic simulation. It was experimentally found that the SNP variants of SMUG1, N244S and N248Y, had increased catalytic activity compared to the wild-type enzyme, probably due to the acceleration of the dissociation of the enzyme-product complex and an increase in the enzyme turnover rate. All other SNP variants of SMUG1 (G90C, P240H) and MBD4^(cat), in which amino acid substitutions disrupted the substrate binding region and/or active site, had significantly lower catalytic activity than the wild-type enzymes.