Evaluating the implementation of family-centered substance use treatment for pregnant and postpartum people: A mixed-methods study.

INTRODUCTION: Family-centered substance use treatment (FCSUT) approaches for pregnant and postpartum people have the potential to prevent intergenerational transmission of adverse childhood experiences (ACEs). Guided by two theoretical frameworks drawn from implementation science (the Consolidated Framework for Implementation Research [CFIR] and the Reach, Effectiveness, Adoption, Implementation and Maintenance [RE-AIM] framework), this study used a mixed methods approach to answer: (1) What is the extent to which FCSUT approaches are offered for pregnant and postpartum people seeking substance use disorder (SUD) treatment? and (2) How are FCSUT approaches for pregnant and postpartum people implemented? METHODS: This study utilized a sequential mixed methods design that began with quantitative data collection followed by qualitative data collection. The quantitative component consisted of service provision surveys of facilities that provided FCSUT to pregnant and postpartum people (n = 118). The qualitative component consisted of semi-structured in-depth interviews with administrators and providers working at FCSUT facilities (n = 26) and pregnant and postpartum people who were currently receiving or had previously received services in the last two years from FCSUT facilities (n = 27). The qualitative findings were used to deepen understanding of the quantitative findings. RESULTS: Findings from the quantitative survey of treatment facilities' FCSUT provision revealed that while most facilities offered services related to substance use treatment, behavioral health, and parenting skills development or parent training, a smaller proportion offered services related to prenatal and postpartum health, sexual and reproductive health, and family-related services. Qualitative in-depth interviews with program administrators and providers and pregnant and postpartum people who had participated in FCSUT programs revealed major themes around expanding reach of facilities by maintaining participants' familial connections, resources for implementation and maintenance of FCSUT, the importance of program adaptation, and gaps in service delivery. CONCLUSIONS: Results indicated there is a wide range of FCSUT services offered at treatment facilities across the United States. Furthermore, while many pregnant and postpartum people expressed positive experiences with FCSUT, there are some areas that should be considered for future progress to be made.

Examining the Biological Impacts of Parent-Child Relationship Dynamics on Preschool-Aged Children who have Experienced Adversity.

Parent-child relationship dynamics have been shown to predict socioemotional and behavioral outcomes for children, but little is known about how they may affect biological development. The aim of this study was to test if observational assessments of parent-child relationship dynamics (cohesion, enmeshment, and disengagement) were associated with three biological indices of early life adversity and downstream health risk: (1) methylation of the glucocorticoid receptor gene (NR3C1), (2) telomere attrition, and (3) mitochondrial biogenesis, indexed by mitochondrial DNA copy number (mtDNAcn), all of which were measured in children's saliva. We tested hypotheses using a sample of 254 preschool-aged children (M age = 51.04 months) with and without child welfare-substantiated maltreatment (52% with documented case of moderate-severe maltreatment) who were racially and ethnically diverse (17% Black, 40% White, 23% biracial, and 20% other races; 45% Hispanic) and from primarily low-income backgrounds (91% qualified for public assistance). Results of path analyses revealed that: (1) higher parent-child cohesion was associated with lower levels of methylation of NR3C1 exon 1D and longer telomeres, and (2) higher parent-child disengagement was associated with higher levels of methylation of NR3C1 exon 1D and shorter telomeres. Results suggest that parent-child relationship dynamics may have distinct biological effects on children.

Detection of a Geminate Photoproduct of Bovine Cytochrome c Oxidase by Time-Resolved Serial Femtosecond Crystallography.

Cytochrome c oxidase (CcO) is a large membrane-bound hemeprotein that catalyzes the reduction of dioxygen to water. Unlike classical dioxygen binding hemeproteins with a heme b group in their active sites, CcO has a unique binuclear center (BNC) composed of a copper atom (CuB) and a heme a3 iron, where O2 binds and is reduced to water. CO is a versatile O2 surrogate in ligand binding and escape reactions. Previous time-resolved spectroscopic studies of the CO complexes of bovine CcO (bCcO) revealed that photolyzing CO from the heme a3 iron leads to a metastable intermediate (CuB-CO), where CO is bound to CuB, before it escapes out of the BNC. Here, with a pump-probe based time-resolved serial femtosecond X-ray crystallography, we detected a geminate photoproduct of the bCcO-CO complex, where CO is dissociated from the heme a3 iron and moved to a temporary binding site midway between the CuB and the heme a3 iron, while the locations of the two metal centers and the conformation of Helix-X, housing the proximal histidine ligand of the heme a3 iron, remain in the CO complex state. This new structure, combined with other reported structures of bCcO, allows for a clearer definition of the ligand dissociation trajectory as well as the associated protein dynamics.

Detection of a geminate photoproduct of bovine cytochrome c oxidase by time-resolved serial femtosecond crystallography.

Cytochrome c oxidase (C c O) is a large membrane-bound hemeprotein that catalyzes the reduction of dioxygen to water. Unlike classical dioxygen binding hemeproteins with a heme b group in their active sites, C c O has a unique binuclear center (BNC) comprised of a copper atom (Cu B ) and a heme a 3 iron, where O 2 binds and is reduced to water. CO is a versatile O 2 surrogate in ligand binding and escape reactions. Previous time-resolved spectroscopic studies of the CO complexes of bovine C c O (bC c O) revealed that photolyzing CO from the heme a 3 iron leads to a metastable intermediate (Cu B -CO), where CO is bound to Cu B , before it escapes out of the BNC. Here, with a time-resolved serial femtosecond X-ray crystallography-based pump-probe method, we detected a geminate photoproduct of the bC c O-CO complex, where CO is dissociated from the heme a 3 iron and moved to a temporary binding site midway between the Cu B and the heme a 3 iron, while the locations of the two metal centers and the conformation of the Helix-X, housing the proximal histidine ligand of the heme a 3 iron, remain in the CO complex state. This new structure, combined with other reported structures of bC c O, allows the full definition of the ligand dissociation trajectory, as well as the associated protein dynamics.

Maternal perinatal hypertensive disorders and parenting in infancy.

Maternal mental health strongly influences parenting during infancy. However, it is unclear whether maternal physical health conditions in the perinatal period may also impact parenting. Examining the association of hypertensive disorders - a common physical health problem in pregnancy - with subsequent parenting behaviors is an important first step in understanding the connection between maternal physical health and parenting during this critical developmental period. This study evaluated whether hypertensive disorders of pregnancy (HDP) and hypertensive disorders (HD) diagnosed after the birth of the infant were associated with parenting self-efficacy, parenting stress, and observed parental responsiveness during mother-infant interactions at 6 and 12 months postpartum among a sample of racially and ethnically diverse mothers and their infants (N = 295). Results showed that mothers with an HDP or HD diagnosis had lower levels of parenting self-efficacy, higher levels of parenting stress, and lower levels of observed parental responsiveness compared to mothers without an HDP or HD diagnosis. Given that women with childhood adversity are at higher risk for experiencing HDP/HD and may have more difficulties with parenting compared to women without childhood adversity, we utilized a sample of mothers wherein most had experienced at least one form of adversity in their childhoods. Exploratory analyses revealed that HDP/HD moderated the relation between early life experiences and parenting outcomes in all but one model. Associations between HDP/HD and parenting are discussed, with implications for how we understand maternal physical health as a determinant of parenting in the perinatal period.

Understanding links between maternal perinatal posttraumatic stress symptoms and infant socioemotional and physical health.

Maternal posttraumatic stress symptoms (PTSS) are associated with adverse consequences for older children, but very few studies have examined links between perinatal maternal PTSS and infant outcomes. Trauma exposure and psychopathology, including PTSS, is often heightened for women during pregnancy through 1 year postpartum. Therefore, the perinatal period may be a critical time for understanding the risk maternal PTSS and other mental health factors pose to the socioemotional and physical health of infants. The present study explored the relation between maternal PTSS and infant socioemotional and physical health problems in a sample of racially and ethnically diverse mother-infant dyads (N = 295) assessed prenatally and at 12 months postpartum. This study also examined whether there are: (1) moderating effects of maternal depressive symptoms and parenting stress on these associations and (2) indirect effects of PTSS on infant outcomes through observed maternal sensitivity. Results indicated that postpartum depressive symptoms and parenting stress, rather than PTSS, were associated with greater infant socioemotional health problems. However, prenatal PTSS were associated with greater infant physical health problems when mothers also reported clinically significant levels of postpartum depressive symptoms. Maternal sensitivity was not associated with maternal PTSS, depressive symptoms, or parenting stress, nor was it related to infant socioemotional and physical health; thus, maternal sensitivity was not tested as an intermediary mechanism linking maternal mental health with infant outcomes. Implications for promoting maternal mental health in the perinatal period to bolster socioemotional and physical health of infants are discussed.

Los síntomas de estrés materno postraumático (PTSS) se asocian con consecuencias adversas para niños de mayor edad, pero pocos estudios han examinado las conexiones entre PTSS materno perinatal y los resultados en el infante. El estar expuesta al trauma y la sicopatología de este, incluyendo PTSS, a menudo se intensifican más en el caso de mujeres durante el embarazo y hasta un año después del parto. Por tanto, el período perinatal pudiera ser un omento crítico para comprender el riesgo que el PTSS materno y otros factores de salud mental presentan para la salud socioemocional y física de los infantes. Este estudio exploró la relación entre el PTSS materno y los problemas de salud socioemocional y física del infante en un grupo muestra de díadas madre-infante racial y étnicamente diversas (N = 295), evaluadas prenatalmente y a los 12 meses después del parto. Este estudio también examinó si hay: (1) efectos moderadores de los síntomas depresivos maternos y el estrés de crianza sobre estas asociaciones y (2) efectos indirectos de PTSS sobre los resultados en el infante a través de la observada sensibilidad materna. Los resultados indican que los síntomas depresivos y el estrés de crianza, en vez de PTSS, estaban asociados con mayores problemas de salud socioemocional del infante. Sin embargo, el PTSS se asoció con mayores problemas de salud física en el infante cuando las madres también reportaron niveles clínicamente significativos de síntomas depresivos. No se corroboró el que la sensibilidad materna fuera un mecanismo intermediario de conexión entre PTSS y otros factores de salud mental materna y resultados en el infante.

Les symptômes des stress posttraumatique (SPT) maternel sont liés à des conséquences adverses pour les enfants plus âgés mais peu d'études ont examiné les liens entre le SPT périnatal maternel et les résultats sur les nourrissons. L'exposition au trauma et la psychopathologie, y compris le SPT, est souvent accrues pour les femmes durant la grossesse jusqu'à un an après la naissance. Par conséquent la période périnatale peut être un moment critique pour la compréhension du risque que posent le SPT maternel et d'autres facteurs de santé mentale à la santé socio-émotionnelle et physique des nourrissons. Cette étude a exploré la relation entre le SPT maternel et les problèmes socio-émotionnels et physiques des nourrissons chez un échantillon de dyades mère-nourrisson racialement et ethniquement diverses (N = 295) évaluées au stade prénatal et à 12 mois après la naissance. Cette étude a aussi examiné s'il existait : (1) des effets modérateurs de symptômes dépressifs maternels et du stress de parentage sur ces associations et (2) des effets indirects de SPT sur les résultats du nourrisson à travers une sensibilité maternelle observée. Les résultats ont indiqué que les symptômes dépressifs postpartum et le stress de parentage, plus que le SPT, étaient liés à des problèmes plus élevés de santé socio-émotionnels du nourrisson. Cependant le SPT prénatal était lié à de plus grands problèmes de santé physique du nourrisson quand les mères faisaient aussi état de niveaux cliniquement élevés de symptômes dépressifs postpartum. La sensibilité maternelle n'était pas liée au SPT maternel, aux symptômes dépressifs ou au stress de parentage, et n'était pas non plus liée à la santé socio-émotionnelle et physique du nourrisson. Donc la sensibilité maternelle n'a pas testée comme mécanisme intermédiaire liant la santé mentale maternelle aux résultats du nourrisson. Les implications pour la promotion de la santé mentale maternelle dans la période périnatale afin de soutenir la santé socio-émotionnelle et physique des nourrissons sont discutées.

Family origins of distinct forms of children's involvement in interparental conflict.

Previous research has highlighted the value in parsing unidimensional assessments of children's involvement in interparental conflict into distinct forms for advancing an understanding of children's development; however, little is known about the underlying antecedents of distinct forms of involvement. The present study provides the first systematic analysis of the interparental conflict and parenting predictors of residualized change in maternal reports of three forms of children's involvement in interparental conflict (i.e., cautious, caregiving, coercive). Participants in this multimethod, multi-informant longitudinal study included 243 preschool children (Mage = 4.60 years), mothers, and their partners from racially, ethnically, and socioeconomically diverse backgrounds. Multivariate analyses demonstrated selectivity in links between interparental conflict and parenting and children's involvement in interparental conflict. Findings from the interparental conflict analyses revealed that Wave 1 constructive conflict uniquely predicted lower Wave 2 cautious involvement, and Wave 1 hostile conflict uniquely predicted greater Wave 2 coercive involvement. Findings from the parenting analyses indicated that Wave 1 maternal responsiveness uniquely predicted lower Wave 2 cautious involvement and Wave 1 maternal vulnerability uniquely predicted greater Wave 2 coercive involvement. Although interparental conflict and parenting antecedents did not predict caregiving involvement, a series of follow-up analyses individually examining each form of interparental conflict and parenting as a predictor of children's involvement revealed that greater Wave 2 caregiving involvement was predicted by higher levels of Wave 1 disengaged conflict and lower levels of Wave 1 constructive conflict. Findings are interpreted in the context of developmental psychopathology models that emphasize children's response patterns to family adversity. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Maternal and paternal unsupportive parenting and children's externalizing symptoms: The mediational role of children's attention biases to negative emotion.

This study examined children's duration of attention to negative emotions (i.e., anger, sadness, fear) as a mediator of associations among maternal and paternal unsupportive parenting and children's externalizing symptoms in a sample of 240 mothers, fathers, and their preschool children (Mage = 4.64 years). The multimethod, multi-informant design consisted of three annual measurement occasions. Analysis of maternal and paternal unsupportive parenting as predictors in latent difference changes in children's affect-biased attention and behavior problems indicated that children's attention to negative emotions mediated the specific association between maternal unsupportive parenting and children's subsequent increases in externalizing symptoms. Maternal unsupportive parenting at Wave 1 predicted decreases in children's attention to negative facial expressions of adults from Wave 1 to 2. Reductions in children's attention to negative emotion, in turn, predicted increases in their externalizing symptoms from Wave 1 to 3. Additional tests of children's fearful distress and hostile responses to parental conflict as explanatory mechanisms revealed that increases in children's fearful distress reactivity from Wave 1 to 2 accounted for the association between maternal unsupportive parenting and concomitant decreases in their attention to negative emotions. Results are discussed in the context of information processing models of family adversity and developmental psychopathology.

Beyond destructive and constructive interparental conflict: Children's psychological vulnerability to interparental disorganization.

Guided by models of family unpredictability, this study was designed to identify the distinctive sequelae of disorganized interparental conflict, a dimension of interparental conflict characterized by abrupt, inexplicable changes in parental emotional lability, conflict tactics, and verbalizations. Participants included 208 kindergarten children (M age = 5.74 years; 56% girls), mothers, and their caregiving partners from racially diverse backgrounds (e.g., 44% Black) who participated in a longitudinal study with two annual measurement occasions. At Wave 1, trained observers assessed disorganized interparental conflict. Observational and survey assessments were used to assess several family (i.e., interparental conflict, parenting difficulties, parent psychopathology, family instability) and demographic (i.e., children's gender, household income, parent education) characteristics. Assessments of child functioning at each wave included psychological adjustment (i.e., externalizing and internalizing symptoms, prosocial behavior), social information processing difficulties, and attention to emotion cues. Findings from structural equation modeling analyses indicated disorganized interparental conflict significantly predicted decreases in children's prosocial behavior and increases in their externalizing problems, angry reactivity to social problems, and biased attention to angry and sad cues over a one-year period. Results were significant while controlling for established measures of interparental conflict, parenting difficulties, parent psychopathology, family instability, and demographic characteristics. The findings suggest that disorganized characteristics of interparental conflict may be an important domain of clinical change beyond the established targets of family harshness and adversity. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Children's dove temperament as a differential susceptibility factor in child rearing contexts.

This multistudy article examines whether children's susceptibility to their socialization experiences varies as a function of their dove temperament dispositions, an evolutionarily informed pattern of traits marked by a low threshold of environmental stimulation and greater behavioral flexibility across environmental contexts. Participants in Study 1 consisted of 70 mothers and their 4- to 6-year-old children: M age = 4.79 years; 57% girls; 33% Black or multiracial; 14% Latinx; median annual income range = $55,000 - $74,999. For Study 2, participants were 243 families, including mothers, fathers, and preschool children: M age = 4.60 years; 56% girls; 54% Black or multiracial, 16% Latinx; median annual income = $36,000). The studies used multimethod, multiinformant measurement batteries within a cross-sectional design (i.e., Study 1) or longitudinal design with three annual measurement occasions (i.e., Study 2). Study 1 findings indicated that associations among maternal parenting quality and psychological problems were only significant for children who were high in dove temperament. Consistent with these findings, Study 2 latent growth curve analyses showed that children experiencing high family adversity (i.e., maternal and paternal parenting difficulties, interparental conflict) were more susceptible to subsequent internalizing and social problems only when they were high in dove temperament. Supporting its role as a susceptibility factor, findings revealed that children with dove temperaments evidenced lower levels of psychological problems under supportive family conditions and higher psychological difficulties in adverse family contexts. Analyses further showed that the composition and moderating effects of dove temperament were distinct from other temperamental susceptibility candidates. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cascades of Risk Linking Intimate Partner Violence and Adverse Childhood Experiences to Less Sensitive Caregiving During Infancy.

This study evaluated if maternal intimate partner violence (IPV) had indirect effects on sensitive parenting in infancy through prenatal depressive symptoms and postpartum parenting stress and if maternal adverse childhood experiences (ACEs) moderated these indirect effects. We hypothesized that: (a) IPV would be associated with greater prenatal depressive symptoms, which would predict greater postpartum parenting stress, and ultimately less sensitive parenting and (b) the link between IPV and depressive symptoms would be strongest for mothers with high ACEs. Participants included 295 mothers and their infants who were assessed prenatally and at 12 months postpartum. Path analyses indicated that mothers with higher IPV endorsed greater prenatal depressive symptoms, which was in turn associated with postpartum parenting stress, and ultimately less sensitive parenting behavior. Moderation analyses revealed that these indirect effects varied as a function of maternal ACEs, with the link between IPV and depressive symptoms only present for mothers who reported high ACEs. Because less sensitive caregiving is often an early indicator of child maltreatment risk, understanding precursors to sensitivity is critical to increase precision in parenting interventions designed to reduce risk for maltreatment. Results may inform evidence-based preventive interventions for mothers and infants at high-risk for child abuse and neglect.

Intergenerational Effects of Maternal Childhood Experiences on Maternal Parenting and Infant Developmental Progress.

OBJECTIVE: This study evaluated the intergenerational indirect effects of maternal childhood experiences on infant progress in reaching developmental milestones through maternal scaffolding behaviors. We hypothesized that mothers who perceived their own mothers as highly supportive in childhood, even in the context of adverse childhood experiences (ACEs), would be more likely to engage in scaffolding with their infants, which in turn would predict greater infant developmental progress (e.g., less risk for developmental delay). METHODS: Participants included 295 low-income mothers and their infants who were assessed prenatally and at 6 and 12 months postpartum. Mothers retrospectively reported on their childhood experiences, maternal parenting behaviors were observationally rated at 6 months postpartum, and infant developmental progress (communication, problem-solving, gross motor, fine motor, and personal-social) was assessed at 6 and 12 months postpartum using the Ages and Stages Questionnaire. RESULTS: The results of autoregressive structural equation models indicated that mothers who perceived their own mothers as highly supportive in childhood were more likely to engage in scaffolding behaviors with their infants, who in turn made greater progress (e.g., showed less risk for developmental delay) in reaching developmental milestones from 6 to 12 months postpartum. Follow-up analyses revealed that indirect effects were specific to infant problem-solving and communication skills. Maternal ACEs were not associated with parenting or infant developmental progress. CONCLUSION: Parenting behaviors in 1 generation influence parenting behaviors in the next, which has implications for infant developmental progress. The results may inform evidence-based preventive interventions for mothers and infants living in contexts of risk.

Segmented flow generator for serial crystallography at the European X-ray free electron laser.

Serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) allows structure determination of membrane proteins and time-resolved crystallography. Common liquid sample delivery continuously jets the protein crystal suspension into the path of the XFEL, wasting a vast amount of sample due to the pulsed nature of all current XFEL sources. The European XFEL (EuXFEL) delivers femtosecond (fs) X-ray pulses in trains spaced 100 ms apart whereas pulses within trains are currently separated by 889 ns. Therefore, continuous sample delivery via fast jets wastes >99% of sample. Here, we introduce a microfluidic device delivering crystal laden droplets segmented with an immiscible oil reducing sample waste and demonstrate droplet injection at the EuXFEL compatible with high pressure liquid delivery of an SFX experiment. While achieving ~60% reduction in sample waste, we determine the structure of the enzyme 3-deoxy-D-manno-octulosonate-8-phosphate synthase from microcrystals delivered in droplets revealing distinct structural features not previously reported.

Household Chaos Moderates Indirect Pathways Involving Domestic Violence, Parenting Practices, and Behavior Problems among Preschool Children.

PURPOSE: This study examined the moderating role of household chaos in indirect pathways involving domestic violence (DV), parenting practices (punitive discipline and responsive), and preschool children's internalizing and externalizing symptoms. We hypothesized that high levels of household chaos would amplify links between domestic violence and parenting difficulties, and that parenting difficulties would in turn predict child behavior problems. METHOD: Participants in this multimethod (survey, semi-structured interview, child protection records) study included 274 preschool children (M age = 50.86 months) and their primary caregivers who were assessed in the home at two time-points spaced 6 months apart. Child welfare documentation of moderate-severe maltreatment within the last 6 months was present for 52% of children, 44% were in households characterized by DV, and most families qualified for public assistance. Hypotheses were tested using path analysis with manifest variables within a structural equation modeling framework. RESULTS: All models provided excellent fit to the data. DV was associated with punitive discipline practices only when household chaos was high. Punitive discipline practices in turn predicted greater child externalizing symptoms 6 months later. Follow-up analyses revealed that the moderating role of chaos was specific to DV, rather than general to other forms of adversity (child maltreatment, lifetime contextual stressors, traumatic events). This interaction between DV and chaos was salient even when controlling for exposure to other adversities and demographic covariates. CONCLUSIONS: Results point to multiple potential targets of intervention that may ultimately buffer children from the risk posed by experiencing DV in the home.

Children's attentional biases to emotions as sources of variability in their vulnerability to interparental conflict.

Little is known about the role children's processing of emotions plays in altering children's vulnerability to interparental conflict. To address this gap, the present study examined whether the mediational cascade involving children's exposure to interparental conflict, their insecure responses to interparental conflict, and their psychological problems varied as a function of children's preexisting biases to attend to angry, fearful, sad, and happy expressions. Participants included 243 children (M age = 4.60 years) and their parents assessed at 3 annual measurement occasions. Moderated-mediation analyses within a cross-lagged autoregressive design indicated that the indirect paths among interparental conflict, emotional insecurity, and psychological problems were significant for children who exhibited greater attentional biases toward angry and fearful emotions. Greater attention to anger and fear specifically moderated the first link in the mediational path. Interparental conflict was a significantly stronger predictor of emotional insecurity for children who attended to angry and fearful cues longer. Consistent with environmental sensitivity theories, children with attentional biases to angry and fearful emotions exhibited disproportionately higher levels of emotional insecurity following exposure to heightened interparental conflict but also lower levels of emotional insecurity after experiencing minimal interparental conflict. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Detouring in the family system as an antecedent of children's adjustment problems.

Guided by conceptualizations of relational boundaries from family systems theory, this study examined unique links between detouring (e.g., alliance between parents against child) and young children's psychological functioning after accounting for general family negativity and conflict. Participants in this longitudinal (i.e., 2 annual waves of data collection), multimethod (i.e., observation, survey, semistructured interview), multiinformant (i.e., parent, teacher, observer) study included 218 young children (mean [M] age = 5.76 years) and their families. The findings from cross-lagged panel analysis indicated that detouring uniquely predicted increases in children's externalizing problems, hostile attribution bias, and peer rejection and victimization over a 1-year period (i.e., the transition from kindergarten to first grade). Conversely, the findings failed to support a child effects model in that child adjustment problems did not predict increases in detouring or family negativity and conflict over time. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

XFEL and NMR Structures of Francisella Lipoprotein Reveal Conformational Space of Drug Target against Tularemia.

Francisella tularensis is the causative agent for the potentially fatal disease tularemia. The lipoprotein Flpp3 has been identified as a virulence determinant of tularemia with no sequence homology outside the Francisella genus. We report a room temperature structure of Flpp3 determined by serial femtosecond crystallography that exists in a significantly different conformation than previously described by the NMR-determined structure. Furthermore, we investigated the conformational space and energy barriers between these two structures by molecular dynamics umbrella sampling and identified three low-energy intermediate states, transitions between which readily occur at room temperature. We have also begun to investigate organic compounds in silico that may act as inhibitors to Flpp3. This work paves the road to developing targeted therapeutics against tularemia and aides in our understanding of the disease mechanisms of tularemia.

Molecular markers of neuroendocrine function and mitochondrial biogenesis associated with early life stress.

OBJECTIVE: Glucocorticoid receptor gene (NR3C1) promoter methylation influences cellular expression of the glucocorticoid receptor and is a proposed mechanism by which early life stress impacts neuroendocrine function. Mitochondria are sensitive and responsive to neuroendocrine stress signaling through the glucocorticoid receptor, and recent evidence with this sample and others shows that mitochondrial DNA copy number (mtDNAcn) is increased in adults with a history of early stress. No prior work has examined the role of NR3C1 methylation in the association between early life stress and mtDNAcn alterations. METHODS: Adult participants (n = 290) completed diagnostic interviews and questionnaires characterizing early stress and lifetime psychiatric symptoms. Medical conditions, active substance abuse, and prescription medications other than oral contraceptives were exclusionary. Subjects with a history of lifetime bipolar, obsessive-compulsive, or psychotic disorders were excluded; individuals with other forms of major psychopathology were included. Whole blood mtDNAcn was measured using qPCR; NR3C1 methylation was measured via pyrosequencing. Multiple regression and bootstrapping procedures tested NR3C1 methylation as a mediator of effects of early stress on mtDNAcn. RESULTS: The positive association between early adversity and mtDNAcn (p = .02) was mediated by negative associations of early adversity with NR3C1 methylation (p = .02) and NR3C1 methylation with mtDNAcn (p < .001). The indirect effect involving early adversity, NR3C1 methylation, and mtDNAcn was significant (95 % CI [.002, .030]). CONCLUSIONS: NR3C1 methylation significantly mediates the association between early stress and mtDNAcn, suggesting that glucocorticoid receptor signaling may be a mechanistic pathway underlying mtDNAcn alterations of interest for future longitudinal work.

Author Correction: Membrane protein megahertz crystallography at the European XFEL.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Coparental discord and children's behavior problems: Children's negative family representations as an explanatory mechanism.

This study examined children's insecure representations of the family as a mechanism accounting for the association between coparental discord and children's externalizing problems in a diverse sample of 243 preschool children (mean [M] age = 4.60 years). The results from a multimethod, multi-informant, prospective design indicated that coparental discord was indirectly related to children's externalizing behaviors through their insecure representations of the family. Higher levels of coparental discord were specifically linked with more insecure representations of the family, which in turn predicted higher levels of externalizing behaviors 2 years later. These pathways remained robust even after considering the roles of general family adversity, child gender, and family income per capita as predictors in the analyses. (PsycInfo Database Record (c) 2020 APA, all rights reserved).