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Nuclear magnetic resonance (NMR) methods that quantitatively probe motions on molecular and atomic levels have propelled the understanding of biomolecular processes for which static structures cannot provide a satisfactory description. In this work, we studied the structure and dynamics of the essential 100-kDa eukaryotic 5'â3' exoribonuclease Xrn2. A combination of complementary fluorine and methyl-TROSY NMR spectroscopy reveals that the apo enzyme is highly dynamic around the catalytic center. These observed dynamics are in agreement with a transition of the enzyme from the ground state into a catalytically competent state. We show that the conformational equilibrium in Xrn2 shifts substantially toward the active state in the presence of substrate and magnesium. Finally, our data reveal that the dynamics in Xrn2 correlate with the RNA degradation rate, as a mutation that attenuates motions also affects catalytic activity. In that light, our results stress the importance of studies that go beyond static structural information.
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Exorribonucleases , Flúor , Catálise , Exorribonucleases/genética , Magnésio , Ressonância Magnética Nuclear BiomolecularRESUMO
Doctors' interactional competencies play a crucial role in patient satisfaction, well-being, and compliance. Accordingly, it is in medical schools' interest to select candidates with strong interactional abilities. While Multiple Mini Interviews (MMIs) provide a useful context to assess such abilities, the evaluation of candidate performance during MMIs is not always based on a solid theoretical framework. The newly developed selection procedure "Interactional Competencies - Medical Doctors (IC-MD)" uses an MMI circuit with five simulation patient scenarios and is rated based on the theoretically and empirically grounded construct of emotional availability. A first validation study with N = 70 first-semester medical students took place in 2021. In terms of convergent validity, IC-MD ratings showed strong correlations with simulation patients' satisfaction with the encounter (r =.57) but no association with emotional intelligence measures. IC-MD ratings were not related to high school performance or a cognitive student aptitude test, indicating divergent validity. Inter-rater reliability (ICC = 0.63) and generalizability (Eρ2 = 0.64) were satisfactory. The IC-MD proved to be fair regarding participants' age and gender. Participants with prior work experience in healthcare outperformed those without such experience. Participant acceptance of the procedure were good. The IC-MD is a promising selection procedure capable of assessing interactional competencies relevant to the medical setting. Measures of interactional competencies can complement the use of cognitive selection criteria in medical student admission. The predictive validity of the IC-MD needs to be addressed in future studies.
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Adaptive parent-child interaction plays a major role in healthy child development. Caregiver mental health problems can negatively impact parent-child interaction. In turn, interactional quality is often studied as a predictor of child outcome. However, child characteristics supposedly shape parent-child interactions as well. Given associations between child and caregiver mental health and child temperament, this study aimed at differentiating their effects on dyadic interaction quality in adolescence. Child temperament and character at age 5 were investigated as longitudinal predictors of observed mother-adolescent interactional quality at age 14 in a community sample (N = 76). It was examined whether these effects were independent of maternal and child mental health and earlier dysfunctional interaction. Lower novelty seeking, higher reward dependence, and higher cooperativeness separately predicted higher dyadic interactional quality at age 14. Controlling regressions for dysfunctional interaction at age 5, which was a significant negative predictor of later interactional quality, cancelled out the effects of novelty seeking and cooperativeness. Past or concurrent maternal or child psychopathology did not explain variance in mother-adolescent interaction. Applying backward selection, a model including reward dependence and dysfunctional interaction at age 5 and concurrent maternal stress showed the best fit for explaining dyadic interaction quality. Results suggest that enduring rather than transient child features predict interactional quality in a community sample. Effects of temperament are not better explained by those of psychopathology, but a combination of child, maternal, and dyadic features predicted dyadic behaviour best. Selective prevention should target parenting in the context of challenging child characteristics specifically.
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Saúde Mental , Relações Mãe-Filho , Temperamento , Humanos , Relações Mãe-Filho/psicologia , Feminino , Masculino , Estudos Longitudinais , Pré-Escolar , Adolescente , Mães/psicologia , Criança , Adulto , Poder Familiar/psicologiaRESUMO
Roller bearings are critical components in various mechanical systems, and the timely detection of potential failures is essential for preventing costly downtimes and avoiding substantial machinery breakdown. This research focuses on finding and verifying a robust method that can detect failures early, without creating false positive failure states. Therefore, this paper introduces a novel algorithm for the early detection of roller bearing failures, particularly tailored to high-precision bearings and automotive test bed systems. The featured method (AFI-Advanced Failure Indicator) utilizes the Fast Fourier Transform (FFT) of wideband accelerometers to calculate the spectral content of vibration signals emitted by roller bearings. By calculating the frequency bands and tracking the movement of these bands within the spectra, the method provides an indicator of the machinery's health, mainly focusing on the early stages of bearing failure. The calculated channel can be used as a trend indicator, enabling the method to identify subtle deviations associated with impending failures. The AFI algorithm incorporates a non-static limit through moving average calculations and volatility analysis methods to determine critical changes in the signal. This thresholding mechanism ensures the algorithm's responsiveness to variations in operating conditions and environmental factors, contributing to its robustness in diverse industrial settings. Further refinement was achieved through an outlier detection filter, which reduces false positives and enhances the algorithm's accuracy in identifying genuine deviations from the normal operational state. To benchmark the developed algorithm, it was compared with three industry-standard algorithms: VRMS calculations per ISO 10813-3, Mean Absolute Value of Extremums (MAVE), and Envelope Frequency Band (EFB). This comparative analysis aimed to evaluate the efficacy of the novel algorithm against the established methods in the field, providing valuable insights into its potential advantages and limitations. In summary, this paper presents an innovative algorithm for the early detection of roller bearing failures, leveraging FFT-based spectral analysis, trend monitoring, adaptive thresholding, and outlier detection. Its ability to confirm the first failure state underscores the algorithm's effectiveness.
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Borderline personality disorder (BPD) is known for disruptions in mother-child interaction, but possible underlying patterns of micro-behavior are barely understood. This is the first study examining behavioral dyadic synchrony-the coordinated and reciprocal adaptation of behavior-and regulation on a micro-level and relating it to macro-behavior in mothers with BPD and their toddlers. Twenty-five mothers with BPD and 29 healthy mothers participated with their 18- to 36-month-old toddlers in a frustration-inducing paradigm. Mother and toddler behavior was continuously micro-coded for gaze, affect, and vocalization. Synchrony, operationalized as the simultaneous engagement in social gaze and positive affect, and (co-)regulative behaviors and their contingencies were analyzed and associated with borderline symptom severity, the overall quality of interaction, and child internalizing and externalizing behavioral problems. Dyads with mothers with BPD showed significantly less synchrony compared to dyads with healthy mothers. Low synchrony was associated with high BPD symptom severity and low overall interaction quality. Dyads with BPD used the same amount of regulative behaviors as dyads with healthy mothers. Though both groups equally responded to children's negative emotionality, mothers with BPD were less effective in drawing the dyad back into synchrony. For dyads with BPD, regulative behaviors were negatively associated with child externalizing behaviors. BPD symptomology may reduce the effectiveness of mothers' attempts to attune to their child's needs. An emphasis on synchrony and regulative behaviors may be an important therapeutic target for parenting programs in mothers with BPD.
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Transtorno da Personalidade Borderline , Comportamento Problema , Feminino , Humanos , Pré-Escolar , Lactente , Mães , Relações Mãe-Filho , Relações Interpessoais , Poder FamiliarRESUMO
The 5' messenger RNA (mRNA) cap structure enhances translation and protects the transcript against exonucleolytic degradation. During mRNA turnover, this cap is removed from the mRNA. This decapping step is catalyzed by the Scavenger Decapping Enzyme (DcpS), in case the mRNA has been exonucleolyticly shortened from the 3' end by the exosome complex. Here, we show that DcpS only processes mRNA fragments that are shorter than three nucleotides in length. Based on a combination of methyl transverse relaxation optimized (TROSY) NMR spectroscopy and X-ray crystallography, we established that the DcpS substrate length-sensing mechanism is based on steric clashes between the enzyme and the third nucleotide of a capped mRNA. For longer mRNA substrates, these clashes prevent conformational changes in DcpS that are required for the formation of a catalytically competent active site. Point mutations that enlarge the space for the third nucleotide in the mRNA body enhance the activity of DcpS on longer mRNA species. We find that this mechanism to ensure that the enzyme is not active on translating long mRNAs is conserved from yeast to humans. Finally, we show that the products that the exosome releases after 3' to 5' degradation of the mRNA body are indeed short enough to be decapped by DcpS. Our data thus directly confirms the notion that mRNA products of the exosome are direct substrates for DcpS. In summary, we demonstrate a direct relationship between conformational changes and enzyme activity that is exploited to achieve substrate selectivity.
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Endorribonucleases/metabolismo , RNA Mensageiro/genética , Sequência de Aminoácidos , Cristalografia por Raios X , Endorribonucleases/química , Endorribonucleases/genética , Humanos , Capuzes de RNA/química , Capuzes de RNA/genética , Capuzes de RNA/metabolismo , Estabilidade de RNA , RNA Mensageiro/química , RNA Mensageiro/metabolismoRESUMO
The present study investigated dissociation as a predictor of parenting and a potential mediator in the relationship between early life maltreatment (ELM) and impaired parenting. Mothers reporting moderate to severe sexual and/or physical abuse (assessed with the Childhood Trauma Questionnaire) formed the maltreatment group (n = 58; MG) and were compared to a non-maltreated comparison group (n = 61; CG) 5 months (T1) and 12 months (T2) postpartum. Dissociative symptoms were assessed with the Dissociative Experiences Scale (DES) at T1. Parenting was investigated by self-report questionnaires and behavior observation (Emotional Availability Scales; EA) at T2. Higher dissociation scores significantly predicted more self-reported parental bonding impairment and stress, higher physical abuse risk and less observed maternal sensitivity, non-intrusiveness and a lower total EA-score during mother-child interactions (p < .001 to p < .05). Dissociation mediated the associations between ELM and self-reported parenting, but not the associations between ELM and parenting as observed during mother-child interactions. Our results suggest that maternal dissociative symptoms play a distinct role in the intergenerational transmission of adverse childhood experiences and should therefore be targeted in therapeutic interventions provided for victims of physical/sexual childhood abuse and in preventive family programs.
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Maus-Tratos Infantis , Poder Familiar , Criança , Transtornos Dissociativos , Feminino , Humanos , Relações Mãe-Filho , MãesRESUMO
We examined whether dynamic parent-child RSA synchrony varied by individual differences in child average RSA and parental history of childhood maltreatment (CM), which has been linked to parental behavioral and physiological dysregulation. We also examined whether RSA synchrony was curvilinear, reflecting homeostatic regulation. Synchrony was defined as the dynamic association between parent and child RSA reactivity (change relative to their own mean) within epoch across a challenging task. Eighty-three mother-preschooler and 61 father-preschooler dyads participated. State-trait modeling showed that RSA synchrony was curvilinear such that significant relations were only found at lower and higher child reactivity. Children's higher task average RSA predicted maternal RSA augmentation and lower task average RSA predicted maternal RSA withdrawal, regardless of whether child reactivity in the moment was low or high, suggesting individual differences in child regulatory capacity were associated with dynamic maternal reactivity. When maternal CM history and child average RSA were both higher, mothers showed RSA augmentation. Father-child synchrony was not moderated by child average RSA but greater paternal CM history predicted fathers' greater RSA withdrawal regardless of whether child RSA reactivity was low or high. Findings offer novel insights into the nature and meaning of RSA synchrony with parents at risk.
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Maus-Tratos Infantis , Arritmia Sinusal Respiratória , Criança , Feminino , Humanos , Relações Mãe-Filho , Mães , Relações Pais-Filho , Pais , Arritmia Sinusal Respiratória/fisiologiaRESUMO
Parents and preschoolers show respiratory sinus arrhythmia (RSA) synchrony, but it is unclear how child self-regulation and the dyadic affective climate shape RSA synchrony and how synchrony differs for mothers and fathers. We examined child average RSA, externalizing problems, and dyadic positive affect as moderators of the synchrony of dynamic, within-epoch child and parent RSA reactivity during a challenging task. Mothers (N = 82) and fathers (N = 60) oversampled for familial risk participated with their 3-year-olds. For mothers, when children showed either higher externalizing or lower average RSA, negative RSA synchrony was observed as dynamic coupling of maternal RSA augmentation and child RSA withdrawal, suggesting inadequate support of the child during challenge. However, when children showed both higher externalizing and lower average RSA, indicating greater regulatory difficulties overall, positive synchrony was observed as joint RSA withdrawal. The same patterns were found for father-child RSA synchrony but instead with respect to the moderators of higher externalizing and lower dyadic positive affect. Findings suggest moderators of RSA synchrony differ by parent and shared positive affect plays a robust role in fathers' RSA reactivity and synchrony. Mothers may be more attuned to children's regulatory capacities, whereas fathers may be more influenced by the immediate behavioral context.
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Arritmia Sinusal Respiratória , Autocontrole , Pré-Escolar , Pai , Feminino , Humanos , Masculino , Relações Mãe-Filho/psicologia , Mães/psicologia , Arritmia Sinusal Respiratória/fisiologiaRESUMO
Early life maltreatment (ELM) has severe and lasting effects on the individual, which might also impact the next generation. On an endocrine level, the hypothalamus-pituitary-adrenal axis has been suggested to play an important role in the interplay between ELM and the development of mental disorders. Several studies have revealed that maternal post-awakening cortisol concentration, maternal sensitivity, maternal ELM and psychopathology are associated with children's cortisol levels. We investigated the post-awakening cortisol concentrations in 6- to 11-year-old children (N = 53) whose mothers either had experienced ELM and had developed a lifetime mental disorder (N = 15 ELM and disorder group), had experienced ELM without developing a mental disorder (N = 12 ELM-only group), or had neither experienced ELM nor developed a mental disorder (N = 26 HC-group). Furthermore, we assessed maternal post-awakening cortisol concentrations, maternal psychopathology, and sensitivity. Multilevel analysis revealed higher cortisol at awakening (S1) levels in children of mothers with ELM and disorder. Maternal cortisol at awakening (S1) also predicted the child's cortisol at awakening (S1), and no effect of maternal sensitivity could be found. The current results replicate an attunement of cortisol levels (S1) between mothers and children and suggest an association between the children's endocrine stress system and maternal factors such as ELM and psychopathology.
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Hidrocortisona , Transtornos Mentais , Criança , Humanos , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Instituições AcadêmicasRESUMO
BACKGROUND: Early life maltreatment (ELM), borderline personality disorder (BPD), and major depressive disorder (MDD) have been associated with empathy deficits in different domains. Lack of maternal empathy has also been related to child behavioral problems. As ELM, BPD, and MDD often co-occur, we aimed to identify dissociable effects on empathy due to these three factors. In addition, we aimed to investigate their indirect effects via empathy on child psychopathology. METHODS: We included 251 mothers with and without MDD (in remission), BPD and ELM and their children, aged 5-12. We used the Interpersonal Reactivity Index as a measure of empathy on four different dimensions (personal distress, empathic concern, perspective taking, and fantasy) and the Child Behavior Checklist as a measure of child psychopathology. RESULTS: Having included all three factors (ELM, MDD, BPD) in one analysis, we found elevated personal distress in MDD and BPD, and lower levels of perspective-taking in BPD, but no effects from ELM on any empathy subscales. Furthermore, we found indirect effects from maternal BPD and MDD on child psychopathology, via maternal personal distress. CONCLUSION: The present study demonstrated the dissociable effects of maternal ELM, MDD, and BPD on empathy. Elevated personal distress in mothers with BPD and MDD may lead to higher levels of child psychopathology.
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Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Transtorno da Personalidade Borderline/epidemiologia , Transtornos do Comportamento Infantil/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Empatia , Mães/psicologia , Adulto , Berlim/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
Objectives Assisted reproductive technologies (ART) may be associated with placental abnormalities including placenta previa, umbilical cord abnormalities, and placental abruption. Our study evaluates the relationship between ART and placental abnormalities compared with spontaneously conceived controls. Methods An IRB-approved cohort study was conducted including women who delivered between January 2013 and December 2018. We excluded delivery prior to 23 weeks and known fetal anomalies. Patients were matched with controls (2:1) for parity, age, and mode of delivery. Controls were women who had spontaneously conceived and delivered immediately preceding and following the index delivery. The primary outcome was placental abnormalities found on both antenatal ultrasound and pathology in ART gestations compared with spontaneously conceived gestations. Results There were 120 ART pregnancies and 240 matched control pregnancies identified. The groups were similar for parity, BMI, comorbidities, number of multiples, mode of delivery, and female newborns. The ART group had a higher maternal age (37.1±5 y vs. 30.0±5 y; p<0.001), greater preterm birth (29 vs. 6%; p<0.001), and lower BW (2,928±803 g vs. 3,273±586 g; p<0.001). The ART group had a higher incidence of placenta previa on ultrasound (4.0 vs. 0.4%, p=0.01), adherent placentas at delivery (3 vs. 0% p=0.014), placental abruption (2 vs. 0%; p=0.04), as well as an increased rate of velamentous cord insertion (12 vs. 3%, p<0.001) and marginal cord insertion (28 vs. 15%, p=0.002). ART demonstrated a two-fold likelihood of abnormal placental pathology. Conclusions ART is associated with increased rate of placental abnormalities, including abnormal umbilical cord insertion and increased rates of adherent placentation. This information may be beneficial in planning and surveillance in patients with ART pregnancies.
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Descolamento Prematuro da Placenta , Parto Obstétrico , Placenta Prévia , Técnicas de Reprodução Assistida/estatística & dados numéricos , Ultrassonografia Pré-Natal/métodos , Cordão Umbilical , Descolamento Prematuro da Placenta/diagnóstico , Descolamento Prematuro da Placenta/epidemiologia , Adulto , Índice de Massa Corporal , Comorbidade , Parto Obstétrico/métodos , Parto Obstétrico/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Paridade , Placenta/diagnóstico por imagem , Placenta Prévia/diagnóstico , Placenta Prévia/epidemiologia , Gravidez , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos , Medição de Risco/métodos , Cordão Umbilical/anormalidades , Cordão Umbilical/diagnóstico por imagem , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Early life maltreatment (ELM) has a high risk of transmission across generations, known as "the cycle of abuse." ELM is also an important risk factor for developing mental disorders, and having a mental disorder increases the risk of child abuse. Both the abuse potential in mothers with ELM and in mothers with a history of mental disorders might be associated with a disturbed mother-child interaction. OBJECTIVE: The current study examined differences in emotional availability between mothers with a history of ELM and previous or current mental disorders (non-resilient), mothers with ELM without mental disorders (resilient), and control mothers without ELM and without mental disorders. METHODS: Thirty-three non-resilient mothers, 18 resilient mothers, and 37 control mothers and their 5- to 12-year-old children participated in a standardized mother-child interaction task. Videotaped interactions were rated by three independent, trained raters based on the Emotional Availability Scales (EA Scales) and compared between the groups. RESULTS: The non-resilient mothers and their children showed reduced maternal sensitivity, structuring, non-intrusiveness, non-hostility, responsiveness, and involvement compared to the resilient mothers and their children and the control mothers and their children (p = 0.006, ηp2 = 0.12). No differences on any of the EA Scales were found between resilient mothers and control mothers. CONCLUSIONS: These deficits in mother-child interaction in non-resilient mothers might contribute to mechanisms that could explain the cycle of abuse. Interestingly, resilient mothers, who did not develop a mental disorder despite having experienced ELM, did not show these deficits. Thus, prevention programs promoting resilience might be a key to break the cycle of abuse.
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Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Maus-Tratos Infantis/psicologia , Transtornos Mentais/psicologia , Relações Mãe-Filho/psicologia , Mães/psicologia , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Previous research revealed experiences of childhood adversity (CA) to be related to less favorable parenting behavior. It can further be expected that maternal oxytocin receptor (OXTR) genes may influence parenting behavior and moderate relationships between CA and parenting behavior. Moreover, associations between the OXTR gene and plasma oxytocin (OT) have been discussed. The present study investigated main effects of the OXTR gene on parenting behavior and plasma OT of mothers, and moderating effects of the OXTR gene on the relationship between mothers' experiences of CA and parenting behavior. We relied on a sample of 193 mothers and their on average 8-year-old children. Maternal experiences of CA were assessed using a standardized interview. A questionnaire for the assessment of child abuse potential and observations of mother-child interaction were used as indicators of parenting behavior. For mothers, we analyzed three polymorphisms (rs53576, rs1042778, rs2254298) of the OXTR gene and plasma OT. Only the rs53576 was associated with mothers' parenting behavior, specifically with maternal sensitivity. The rs2254298 significantly moderated relations between mothers' experiences of CA and parenting behavior. Significant relations could be found only for mothers who were homozygous for the G allele. The G allele of the rs2254298 was further related to increased plasma OT levels. Our findings underline the importance of considering genetic variation when investigating consequences of CA and developing intervention programs that are adapted to an individual's needs.
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Adultos Sobreviventes de Eventos Adversos na Infância , Experiências Adversas da Infância , Maus-Tratos Infantis , Comportamento Materno/fisiologia , Relações Mãe-Filho , Ocitocina/sangue , Poder Familiar , Receptores de Ocitocina/genética , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Early life maltreatment (ELM) has long-lasting effects on social interaction. When interacting with their own child, women with ELM often report difficulties in parenting and show reduced maternal sensitivity. Sensitive maternal behavior requires the recognition of the child's emotional state depicted in its facial emotions. Based on previous studies, it can be expected that ELM affects the neural processing of facial emotions by altering activation patterns in parts of the brain's empathy and mentalizing networks. However, so far studies have focused on the processing of standardized, adult facial emotions. Therefore, the current study investigated the impact of ELM on the processing of one's own child's facial emotions using functional magnetic resonance imaging. To achieve this, 27 mothers with and 26 mothers without a history of ELM (all without current mental disorders and psychopharmacological treatment) took part in an emotional face recognition paradigm with happy, sad, and neutral faces of their own and an unknown primary school-aged child of the same age and sex. We found elevated activations in regions of the mentalizing (superior temporal sulcus, precuneus) and mirror neuron (inferior parietal lobule) networks as well as in the visual face processing network (cuneus, middle temporal gyrus) in mothers with ELM compared to the non-maltreated mothers in response to happy faces of their own child. This suggests a more effortful processing and cognitive empathic mentalizing of the own child's facial happiness in mothers with ELM. Future research should address whether this might indicate a compensatory recruitment of mentalizing capacities to maintain maternal sensitivity.
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Sobreviventes Adultos de Maus-Tratos Infantis , Experiências Adversas da Infância , Mapeamento Encefálico/métodos , Córtex Cerebral/fisiopatologia , Emoções/fisiologia , Reconhecimento Facial/fisiologia , Comportamento Materno/fisiologia , Relações Mãe-Filho , Rede Nervosa/fisiologia , Percepção Social , Teoria da Mente/fisiologia , Adulto , Córtex Cerebral/diagnóstico por imagem , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagemRESUMO
The study addresses the impact of maternal early life maltreatment (ELM) and maternal history of depression (HoD) on offspring's mental health. Maternal sensitivity was examined as a potential mediator explaining the relationship between maternal ELM, maternal HoD and child psychopathology. Participants were 194 mothers with and without HoD and/or ELM as well as their children between 5 and 12 years. Maternal sensitivity was assessed using the Emotional Availability Scales. Parent and teacher ratings were utilized to assess child psychopathology. Path analyses showed an indirect effect of maternal HoD on parents' ratings of child psychopathology with maternal sensitivity as mediating variable. In contrast, maternal ELM was directly linked to teachers' ratings of child psychopathology; this effect was not mediated by maternal sensitivity. Our results indicate that the impact of maternal HoD, maternal ELM, and maternal sensitivity on offspring psychopathology might vary depending on the context in which child psychopathology is assessed.
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Maus-Tratos Infantis/psicologia , Filho de Pais com Deficiência/psicologia , Depressão/psicologia , Comportamento Materno , Transtornos do Neurodesenvolvimento/psicologia , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Mães/psicologia , Apego ao Objeto , Relações Pais-Filho , PsicopatologiaRESUMO
INTRODUCTION: Female sexuality may be affected by many somatic and psychological factors. Somatic conditions have impact on psychological well-being. We assumed that chronic disease like Irritable Bowel Syndrome (IBS), when producing the long-term distress, may greatly influence sexual functioning. AIM: The aim of this study was to determine whether the severity of IBS influences sexual functions of women and take into consideration other factors like Small Intestinal Bacterial Overgrowth (SIBO) comorbidity and duration of IBS. SUBJECTS AND METHODS: Study patients were recruited by contacting IBS patients at Gastroenterology Ward of Clinical University Centre in Katowice. The survey consisted of 3 parts. The first part were socio-demographic questions. The second part was polish translation of Female Sexuality Functions Index (FSFI) questionnaire. The third part consisted of questions about the patient condition, pharmacotherapy and Irritable Bowel Syndrome Severity Score (IBSSS) questionnaire. 307 women were included in the study and completed the questionnaire. 143 participants were diagnosed with IBS. The mean age of participants was 27 (IQR=23-33). 29% of the patients (n=41) had severe, 47% (n=68) moderate and 24% (n=34) mild IBS. RESULTS: The prevalence of sexual dysfunctions was greater in women with IBS (48%) than in healthy control group (23%) (p<0.001). The median of FSFI was: 30.1 (26.3-32.8) for healthy control group, 30 (23.5-32.6) for mild IBS, 26.2 (22.2-31.6) for moderate and 24.4 (20.1-28.9) for severe. CONCLUSION: IBS decreases all domains of women sexual activity. Severity of sexual dysfunctions relate to intensity of IBS symptoms. All physicians treating IBS-patients should take sexual dysfunctions into their clinical consideration.
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Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/psicologia , Disfunções Sexuais Fisiológicas/complicações , Disfunções Sexuais Psicogênicas/complicações , Sexualidade/psicologia , Infecções Bacterianas/complicações , Infecções Bacterianas/microbiologia , Infecções Bacterianas/fisiopatologia , Feminino , Humanos , Intestinos/microbiologia , Intestinos/fisiopatologia , Síndrome do Intestino Irritável/microbiologia , Disfunções Sexuais Fisiológicas/fisiopatologia , Disfunções Sexuais Fisiológicas/psicologia , Disfunções Sexuais Psicogênicas/fisiopatologia , Disfunções Sexuais Psicogênicas/psicologiaRESUMO
The eukaryotic mRNA 5' cap structure is indispensible for pre-mRNA processing, mRNA export, translation initiation, and mRNA stability. Despite this importance, structural and biophysical studies that involve capped RNA are challenging and rare due to the lack of a general method to prepare mRNA in sufficient quantities. Here, we show that the vaccinia capping enzyme can be used to produce capped RNA in the amounts that are required for large-scale structural studies. We have therefore designed an efficient expression and purification protocol for the vaccinia capping enzyme. Using this approach, the reaction scale can be increased in a cost-efficient manner, where the yields of the capped RNA solely depend on the amount of available uncapped RNA target. Using a large number of RNA substrates, we show that the efficiency of the capping reaction is largely independent of the sequence, length, and secondary structure of the RNA, which makes our approach generally applicable. We demonstrate that the capped RNA can be directly used for quantitative biophysical studies, including fluorescence anisotropy and high-resolution NMR spectroscopy. In combination with (13)C-methyl-labeled S-adenosyl methionine, the methyl groups in the RNA can be labeled for methyl TROSY NMR spectroscopy. Finally, we show that our approach can produce both cap-0 and cap-1 RNA in high amounts. In summary, we here introduce a general and straightforward method that opens new means for structural and functional studies of proteins and enzymes in complex with capped RNA.
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Capuzes de RNA/biossíntese , Processamento Pós-Transcricional do RNA , Fator de Iniciação 4E em Eucariotos/metabolismo , Humanos , Metiltransferases/metabolismo , Complexos Multienzimáticos/metabolismo , Nucleotidiltransferases/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Capuzes de RNA/química , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas Virais/metabolismoRESUMO
BACKGROUND: Early-life maltreatment has severe consequences for the affected individual, and it has an impact on the next generation. To improve understanding of the intergenerational effects of abuse, we investigated the consequences of early-life maltreatment on maternal sensitivity and associated brain mechanisms during mother-child interactions. METHODS: In total, 47 mothers (22 with a history of physical and/or sexual childhood abuse and 25 without, all without current mental disorders) took part in a standardized real-life interaction with their 7- to 11-year-old child (not abused) and a subsequent functional imaging script-driven imagery task. RESULTS: Mothers with early-life maltreatment were less sensitive in real-life mother-child interactions, but while imagining conflictual interactions with their child, they showed increased activation in regions of the salience and emotion-processing network, such as the amygdala, insula and hippocampus. This activation pattern was in contrast to that of mothers without early-life maltreatment, who showed higher activations in those regions in response to pleasant mother-child interactions. Mothers with early-life maltreatment also showed reduced functional connectivity between regions of the salience and the mentalizing networks. LIMITATIONS: Region-of-interest analyses, which were performed in addition to whole-brain analyses, were exploratory in nature, because they were not further controlled for multiple comparisons. CONCLUSION: Results suggest that for mothers with early-life maltreatment, conflictual interactions with their child may be more salient and behaviourally relevant than pleasant interactions, and that their salience network is poorly modulated by the brain regions involved in mentalizing processes. This activation pattern offers new insights into the mechanisms behind the intergenerational effects of maltreatment and into options for reducing these effects.
Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Tonsila do Cerebelo/fisiopatologia , Córtex Cerebral/fisiopatologia , Hipocampo/fisiopatologia , Imaginação , Imageamento por Ressonância Magnética , Relações Mãe-Filho/psicologia , Adulto , Estudos de Casos e Controles , Criança , Feminino , Neuroimagem Funcional , Humanos , Masculino , Vias Neurais/fisiopatologia , Adulto JovemRESUMO
The structures of the N,N-dimethylformamide (dmf), N,N-dimethylacetamide (dma), and N,N-dimethylpropionamide (dmp) solvated strontium and barium ions have been determined in solution using large angle X-ray scattering and EXAFS spectroscopy. The strontium ion has a mean coordination number (CN) between 6.2 and 6.8, and the barium ion has a mean CN between 7.1 and 7.8 in these amide solvents. The non-integer numbers indicates that equilibria between different coordination numbers and geometries exist in these systems. Structural information of the alkali, alkaline earth, and selected transition metal and lanthanoid(iii) ions, and the halide ions in water, methanol, ethanol, dimethylsulfoxide, formamide, dmf and dma has been combined with previously reported standard partial molar volumes, V0. The ionic radii and charge densities (charge/ionic volume), and corresponding V0 values have been used to gain information on the relationship between structural and volumetric properties. For the structure-breaking ions, i.e. the alkali metal and halide ions, there is an almost linear relationship between the ionic radius and V0. On the other hand, for the structure-making ions, here the alkaline earth, transition metal and lanthanoid(iii) ions, a linear relationship is observed between the charge density and V0. Solvents with a well-defined bulk structure through hydrogen bonding, specifically, water, methanol and ethanol, will be more contracted through solvation than aprotic solvents, as the space between the solvent molecules is lost as a result of the hydrogen bonding. In this respect, methanol stands out as the most compressed solvent participating in solvation compared to its bulk structure.