Mothers' Perceptions of Their Infants

A mother's perceptions of her infant are a core component of her working model of attachment. Interview methods of assessing mothers' perceptions of their infants, while providing detailed and rich information, are time-intensive in administration and analysis. Therefore, a questionnaire measure would be of value for research and healthcare practice. A 44-item questionnaire was developed to investigate the axes along which maternal models are organized. It was predicted that two primary axes, warmth and invasiveness, would be identified, and questionnaire data were collected from mothers in Great Britain and Hungary. The predicted axes were confirmed and a 14-item short-form questionnaire, with good psychometric properties, was derived

Genetikai hatások a korai kötődés fejlődésében

Bowlby elmélete megjósolta, és a következő évtizedek számos empirikus vizsgálata bizonyította, hogy a korai kötődési viselkedés különféle mintázatainak megjelenését elsősorban a gondozói viselkedés érzékenységének eltérései okozzák. Metaelemzések szerint azonban ezek csak harmadát magyarázzák a kötődési viselkedés varianciájának. A gondozási környezet mellett az 1990-es években felmerült a csecsemők egyéni jellemzőinek, pl. temperamentumának befolyása is a kötődés fejlődésére. A molekuláris genetikai módszerek fejlődése a genetikai vizsgálatok érzékenységének növekedését eredményezte, és 2000-ben kutatócsoportunk publikált elsőként a csecsemőkori kötődés egyéni változatosságának hátterében álló specifikus génhatásokról. Tanulmányunkban áttekintjük, hogy a humán genom projekt eredményeinek köszönhetően miként bővült tudásunk az elmúlt 15 év során. Az áttekintett kutatások fő kérdései, hogy a környezeti tényezők mellett mely gének mely változatai gyakorolnak befolyást a csecsemők kötődési viselkedésére, ezek hogyan befolyásolják a kötődés egyéni változatosságát, s milyen kölcsönhatásban lehetnek a környezeti tényezőkkel. Áttekintjük a bizonyítékokat, amelyek azt sugallják, hogy az idegrendszerben kifejeződő bizonyos gének különböző változatai hozzájárulhatnak a gondozói környezetre való eltérő csecsemőkori érzékenységhez (gén−környezet kölcsönhatások), továbbá hogy a gondozói viselkedés korai eltérései különbözőképpen befolyásolhatják egyes, a kötődés fejlődésében fontos gének működését (epigenetikai hatások). | Bowlby’s theory of attachment predicted, and subsequent empirical research has confirmed, that the development of different patterns of early attachment behaviour primarily depends on variations in the sensitivity of caregiving. However, according to meta-analyses, these caregiving variations account for only a third of the variance in infants’ attachment behaviour. From the 1990s, it has been increasingly recognised that infants’ individual characteristics, such as their temperaments, may influence the development of attachment. Methodological advances in the field of molecular genetics have increased the sensitivity of genetic studies and, in 2000, our research group was the first to publish evidence of specific genetic effects underlying the individual variability of infant attachment behaviour. Below, we review the recent advances in knowledge arising from emerging findings of the Human Genome Project. The main questions addressed by the studies reviewed concern variants of specific genes that may affect infants’ attachment behaviour. They also address the nature of the genetic influences and their potential interplay with environments. We review evidence suggesting that different alleles of specific genes that are preferentially expressed in the brain may contribute to infants’ differential susceptibility to the caregiving environments (gene-environment interactions), and also that early differences in caregiving may differentially influence the expression of genes that are important for attachment development (epigenetic effects)

Validation of the Mothers’ Object Relations Scales Short-form (MORS-SF)

A 14-item questionnaire, MORS-SF, was developed in a previous study to assess mothers’ representations of their infants. It was found to have good psychometric properties, being sufficiently reliable and internally valid to enable the further validation of the instrument with additional independently collected datasets. This paper reports the successful validation of MORS-SF against other measures in both the original Hungarian and British samples and also in new samples in both countries, showing predicted relationships with other measures in the original and the independent validation datasets. It is concluded that this is a valid tool, with uses in research and health practice

Validation of the Mothers’ Object Relations Scales Short-form (MORS-SF)

A 14-item questionnaire, MORS-SF, was developed in a previous study to assess mothers’ representations of their infants. It was found to have good psychometric properties, being sufficiently reliable and internally valid to enable the further validation of the instrument with additional independently collected datasets. This paper reports the successful validation of MORS-SF against other measures in both the original Hungarian and British samples and also in new samples in both countries, showing predicted relationships with other measures in the original and the independent validation datasets. It is concluded that this is a valid tool, with uses in research and health practice

A genetic study based on PCNA-ubiquitin fusions reveals no requirement for PCNA polyubiquitylation in DNA damage tolerance

Post-translational modifications of Proliferating Cell Nuclear Antigen (PCNA) play a key role in regulating the bypass of DNA lesions during DNA replication. PCNA can be monoubiquitylated at lysine 164 by the RAD6-RAD18 ubiquitin ligase complex. Through this modification, PCNA can interact with low fidelity Y family DNA polymerases to promote translesion synthesis. Monoubiquitylated PCNA can be polyubiquitylated on lysine 63 of ubiquitin by a further ubiquitin-conjugating complex. This modification promotes a template switching bypass process in yeast, while its role in higher eukaryotes is less clear. We investigated the function of PCNA ubiquitylation using a PCNAK164R mutant DT40 chicken B lymphoblastoma cell line, which is hypersensitive to DNA damaging agents such as methyl methanesulfonate (MMS), cisplatin or ultraviolet radiation (UV) due to the loss of PCNA modifications. In the PCNAK164R mutant we also detected cell cycle arrest following UV treatment, a reduced rate of damage bypass through translesion DNA synthesis on synthetic UV photoproducts, and an increased rate of genomic mutagenesis following MMS treatment. PCNA-ubiquitin fusion proteins have been reported to mimic endogenous PCNA ubiquitylation. We found that the stable expression of a PCNAK164R-ubiquitin fusion protein fully or partially rescued the observed defects of the PCNAK164R mutant. The expression of a PCNAK164R-ubiquitinK63R fusion protein, on which the formation of lysine 63-linked polyubiquitin chains is not possible, similarly rescued the cell cycle arrest, DNA damage sensitivity, reduction of translesion synthesis and increase of MMS-induced genomic mutagenesis. Template switching bypass was not affected by the genetic elimination of PCNA polyubiquitylation, but it was reduced in the absence of the recombination proteins BRCA1 or XRCC3. Our study found no requirement for PCNA polyubiquitylation to protect cells from replication-stalling DNA damage. © 2017 Elsevier B.V

Közös figyelem, atipikus anyai viselkedés és kötődés

Háttér és célok A közös figyelem képességének jellemzően 9 hónapos kori megjelenését követően a csecsemő triádikus (felnőtt—csecsemő—tárgy) interakciók során oszthatja meg a tárgyakkal, eseményekkel kapcsolatos élményeit egy másik személlyel. E képesség fejlődési ütemében megfigyelhető egyéni változatosságot a csecsemő adottságai mellett a gondozói környezet szocio-emocionális jellemzői is befolyásolhatják az interakciók minőségén keresztül. Módszer Kutatásunkban a csecsemők 9 hónapos korában, részben kötött játékhelyzetben figyeltük meg anya—csecsemő párok triádikus helyzet létrehozására irányuló kezdeményező viselkedését, valamint közös fi- gyelmi tevékenységét. A viselkedési jellemzőket az egyéves korban mért kötődés minőségével és az anyai érzelmi kommunikáció atipikusságának mértékével vetettük össze. Eredmények Ahol több párhuzamos (egyszerű) közös figyelem jellemezte az interakciót, ott az anya kevesebb időt töltött passzív monitorozással, viszont többször hívta fel a csecsemő figyelmét a tárgyra dinamikus animálással, és többször pillantott a csecsemő arcára kezdeményezés közben. Ugyanakkor a fejlődésben újabb minőségi lépést jelentő koordinált (megosztott) közös figyelem legerősebb prediktorának a csecsemő összetett, az anya és a tárgy közti tekintetváltással is együtt járó válasza bizonyult. A közös figyelem viselkedések nem függtek össze az anyai atipikus viselkedéssel és a dezorganizált kötődéssel. A párhuzamos — nem koordinált — közös figyelem magas aránya viszont a bizonytalanul kötődő diádok interakciójában volt leginkább jellemző, ami az inszenzitív, a gyermek érdeklődését korlátozó gondozói viselkedés befolyására utalhat. Következtetések A 9 hónapos kori interakciók során megfigyelt koordinált közös figyelem vélhetően inkább a csecsemő fejlődési üteme által meghatározott készségek (pl. tekintetváltogatás), mint az anya egyéni viselkedésének függvénye. Ez magyarázhatja, hogy — ellentétben a párhuzamos közös figyelemmel — a korai koordinált közös figyelem egyéni variabilitása nem mutatott kapcsolatot a kötődés minőségével, amelyet elsősorban a gondozói viselkedés alakít. | Background and aims Infants’ capacity to engage in joint attention emerges at around 9 months of age, and enables the infant to share object- and event-related experiences with a social partner during triadic (adult — infant — object) interactions. Besides maturation, individual differences in development of joint attention skills might also be influenced by the child’s socio-emotional environment through the quality of interactions with the caregivers. Methods Mothers and their 9-month-old infants were observed during semi-structured play. Bids for establishing triadic attention and episodes of dyadic joint attention behaviours were recorded, and associations with the quality of attachment and maternal atypical behaviour assessed at 12 months were tested. Results Longer duration of parallel (simple) joint attention was associated with less passive maternal monitoring, more maternal entertaining initiations (labelled as animation), with more initiations accompanied by looking at the infant’s face. The higher level coordinated (shared) joint attention, on the other hand, was best predicted by the most complex infant response type to a maternal bid, including a gaze shift between the mother and the newly engaged object. Joint attention behaviours were related neither to atypical maternal behaviour nor to disorganised attachment. Above average level of parallel — not coordinated — joint attention, however, characterised interactions of insecurely attached dyads, which might be explained by insensitive caregiving imposing control over the child’s interest and autonomy. Conclusions Coordinated joint attention observed at 9 months of age is more likely to be determined by infants’ developing abilities (e.g., rapid gaze shifts between an object and the partner), than by the variations in mothers’ interactive behaviour. This could explain why individual variability in early coordinated joint attention — as opposed to parallel joint attention — was not associated with the quality of attachment

Two main mutational processes operate in the absence of DNA mismatch repair

The analysis of tumour genome sequences has demonstrated high rates of base substitution mutagenesis upon the inactivation of DNA mismatch repair (MMR), and the resulting somatic mutations in MMR deficient tumours appear to significantly enhance the response to immune therapy. A handful of different algorithmically derived base substitution mutation signatures have been attributed to MMR deficiency in tumour somatic mutation datasets. In contrast, mutation data obtained from whole genome sequences of isogenic wild type and MMR deficient cell lines in this study, as well as from published sources, show a more uniform experimental mutation spectrum of MMR deficiency. In order to resolve this discrepancy, we reanalysed mutation data from MMR deficient tumour whole exome and whole genome sequences. We derived two base substitution signatures using non-negative matrix factorisation, which together adequately describe mutagenesis in all tumour and cell line samples. The two new signatures broadly resemble COSMIC signatures 6 and 20, but perform better than existing COSMIC signatures at identifying MMR deficient tumours in mutation signature deconstruction. We show that the contribution of the two identified signatures, one of which is dominated by C to T mutations at CpG sites, is biased by the different sequence composition of the exome and the whole genome. We further show that the identity of the inactivated MMR gene, the tissue type, the mutational burden or the patient's age does not influence the mutation spectrum, but that a tendency for a greater contribution by the CpG mutational process is observed in tumours as compared to cultured cells. Our analysis suggest that two separable mutational processes operate in the genomes of MMR deficient cells. © 2020 The Author(s