Using the yeast Saccharomyces cerevisiae to uncover regulatory mechanisms of cell surface membrane proteins

Membrane bound organelles define eukaryotic cells. Correct traffic of material between these organelles is crucial for proper cellular function. Arguably one of the most important membranes is the plasma membrane, separating the cell from its external environment. A cell must adapt and respond to its environment, which can change dramatically and rapidly. This is achieved through membrane trafficking mechanisms. The regulation of cell surface membrane proteins in their journey through trafficking pathways and within the plasma membrane itself is not fully understood. As many of these pathways and factors are conserved from yeast to humans, I used the yeast Saccharomyces cerevisiae as a model to uncover mechanistic details about how surface membrane proteins are regulated, with particular focus on cellular responses to nutrients. Following starvation, we detail how yeast cells upregulate endocytosis (Laidlaw et al., 2021) whilst simultaneously downregulating surface recycling (Amoiradaki et al., 2021; Laidlaw et al., 2022b) to drive degradation of surface membrane proteins. Curiously, not all nutrient transporters are degraded in response to starvation, with a small reserve pool being retained in special compartments of the plasma membrane termed eisosomes (Laidlaw et al., 2021). I went on to reveal that during starvation, eisosomes are regulated by dephosphorylation of its core structural subunit (Paine et al., 2022). Beyond this mechanistic work, I also set out to demystify trafficking pathways of surface proteins. I took advantage of the discovery that yeast cells grown in restricted uracil conditions rely on efficient trafficking of a uracil permease for efficient growth. This phenotype allowed me to perform a comprehensive genetic screen to identify and validate many known and novel candidate factors for surface protein trafficking (Paine et al., 2021). In combination, these discoveries represent a significant advance on our understanding of surface protein trafficking and will pave the way for many future studies, in both yeast and in cultured mammalian cell models

Charting the trajectories of adopted children’s emotional and behavioral problems: The impact of early adversity and post-adoptive parental warmth

Children who are adopted from care are more likely to experience enduring emotional and behavioral problems across development; however, adoptees’ trajectories of mental health problems and factors that impact their trajectories are poorly understood. Therefore, we used multilevel growth analyses to chart adoptees’ internalizing and externalizing problems across childhood, and examined the associations between preadoptive risk and postadoptive protective factors on their trajectories. This was investigated in a prospective longitudinal study of case file records (N = 374) and questionnaire-based follow-ups (N = 96) at approximately 5, 21, and 36 months postadoptive placement. Preadoptive adversity (indexed by age at placement, days in care, and number of adverse childhood experiences) was associated with higher internalizing and externalizing scores; the decrease in internalizing scores over childhood was accelerated for those exposed to lower levels of preadoptive risk. Warm adoptive parenting was associated with a marked reduction in children's internalizing and externalizing problems over time. Although potentially limited by shared methods variance and lack of variability in parental warmth scores, these findings demonstrate the deleterious impact of preadoptive risk and the positive role of exceptionally warm adoptive parenting on children's trajectories of mental health problems and have relevance for prevention and intervention strategies

Birth sibling relationships after adoption: the experience of contact with brothers and sisters living elsewhere

We examined how adoptive families manage and respond to contact with children’s birth siblings living elsewhere within a nationally representative sample of 96 families who adopted a child between 01 July 2014 and 31 July 2015. We harnessed prospective, longitudinal data to determine the extent to which plans for contact between adopted children and birth siblings living elsewhere materialised over time. We present adoptive parents’ views and experiences of the contact over four years, together with an analysis of factors that were thought to have prevented, hindered and/or enabled contact between adopted children and their birth siblings. The information shared by the adoptive families illustrates the challenges they faced in promoting sibling contact; in weighing up the complexities associated with managing contact in the short term against the anticipated benefit for their child in the longer term; of balancing a commitment to sibling contact with the psychological needs of their child; and of organising contact within the context of interactions with other families involved and social work professionals. On the basis of these findings, we make recommendations pertaining to the management of both letterbox and face-to-face contact and life story work, and underscore the importance of investing in sibling relationships

Depression and anxiety symptoms of british adoptive parents: a prospective four-wave longitudinal study

The mental health of birth parents has gained attention due to the serious negative consequences for personal, family, and child outcomes, but depression and anxiety in adoptive parents remains under-recognized. Using a prospective, longitudinal design, we investigated anxiety and depression symptoms in 96 British adoptive parents over four time points in the first four years of an adoptive placement. Depression and anxiety symptom scores were relatively stable across time. Growth curve analysis showed that higher child internalizing scores and lower parental sense of competency at five months post-placement were associated with higher initial levels of parental depressive symptoms. Lower parental sense of competency was also associated with higher initial levels of parental anxiety symptoms. Parents of older children and those with higher levels of parental anxiety and sense of competency at five months post-placement had a steeper decrease in depressive symptoms over time. Support for adoptive families primarily focuses on child adjustment. Our findings suggest that professional awareness of parental mental health post-placement may be necessary, and interventions aimed at improving parents’ sense of competency may be beneficial

Adverse childhood experiences of children adopted from care: The importance of adoptive parental warmth for future child adjustment

We investigated the relationship between adverse childhood experiences (ACEs) and children’s internalising symptoms and externalising problems in the Wales Adoption Cohort Study, a prospective longitudinal study that used case file records (n = 374) for a sample of British children adopted from care (M = 2 years, 55% male). Parents (n = 96) completed questionnaires at 3–5 months, 15–17 months, and 31–33 months post-placement. We hypothesised that: (1) children adopted from care would have experienced more ACEs than children in the general population; (2) the number of ACEs would be associated with higher internalising symptom and externalising problem scores; and (3) adoptive parental warmth would moderate the relationship between ACEs and post-placement internalising symptoms and externalising problems. Nearly half (42%) of the children experienced four or more ACEs. Internalising symptoms and externalising problems were significantly higher than the UK general population. The number of ACEs was associated with internalising symptoms 3 years post-adoptive placement but this relationship was moderated by adoptive parental warmth. This study profiles the experiences and characteristics of a national sample of adopted children and highlights the potential importance of parent warmth as a factor that ameliorates the impact of ACEs on poor child outcomes

Adoptive parents’ finances and employment status: a 5-year longitudinal study european child & adolescent psychiatry

We investigated risk and facilitating factors related to families’ change in finances and employment over 5 years following adoption of a child from local authority care in a prospective, longitudinal study of children placed for adoption between 2014 and 2015 (N = 96). Parents completed questionnaires at approximately 5, 21, 36, 48 and 60 months post-placement. We used time series analysis to examine the impact of child (e.g. pre-placement experiences, mental health), family structure (e.g. number of siblings, parent relationship status), and parent (e.g. mental health) factors on change in household income and parent employment status after adoption. We also examined the tendency for parents to comment on employment and finances and the emotional valence of their comments to gauge their concern about their circumstances. Children’s mental health problems were associated with primary caregivers reducing their time spent in employment and parents’ tendency to comment on their financial and work circumstances. Children who experienced more moves in care were more likely to have a primary caregiver not in full-time work, as were children with higher prosocial behaviour scores. Being in full-time work was associated with parents’ symptoms of anxiety. We also detected associations between structural features of the family and changes in income and employment. This study represents one of the first empirical investigations of factors associated with the socioeconomic features of adoptive families’ lives and informs ongoing discussion regarding the support needs of families and the timing, nature, and delivery of post-adoption professional services

Overlapping brain correlates of superior cognition among children at genetic risk for Alzheimer’s disease and/or major depressive disorder

AbstractEarly life adversity (ELA) tends to accelerate neurobiological ageing, which, in turn, is thought to heighten vulnerability to both major depressive disorder (MDD) and Alzheimer’s disease (AD). The two conditions are putatively related, with MDD representing either a risk factor or early symptom of AD. Given the substantial environmental susceptibility of both disorders, timely identification of their neurocognitive markers could facilitate interventions to prevent clinical onset. To this end, we analysed multimodal data from the Adolescent Brain and Cognitive Development study (ages 9–10 years). To disentangle genetic from correlated genetic-environmental influences, while also probing gene-adversity interactions, we compared adoptees, a group generally exposed to substantial ELA, with children raised by their biological families via genetic risk scores (GRS) from genome-wide association studies. AD and MDD GRSs predicted overlapping and widespread neurodevelopmental alterations associated with superior fluid cognition. Specifically, among adoptees only, greater AD GRS were related to accelerated structural maturation (i.e., cortical thinning) and higher MDD GRS were linked to delayed functional neurodevelopment, as reflected in compensatory brain activation on an inhibitory control task. Our study identifies compensatory mechanisms linked to MDD risk and highlights the potential cognitive benefits of accelerated maturation linked to AD vulnerability in late childhood.</jats:p

The neurocognitive profiles of children adopted from care and their emotional and behavioral problems at home and school

Adoptees’ mental health problems in childhood and later life are well described, but little attention has been paid to domestically adopted children’s emotional and behavioral problems and neurocognitive profiles. The aim of this study was to describe the neurocognitive profiles of domestically adopted children in the UK and their parent- and teacher-rated emotional and behavioral problems. Forty-five children (M age = 75.96 months, SD = 12.98; 51.1% female) who were placed for adoption from public care at a M age of 22.14 months (SD = 14.21) completed a battery of age standardized neurocognitive tests, and adoptive parents and school teachers rated their emotional and behavioral problems. Children had more emotional and behavioral problems than the general population and over a fifth scored low (> 1 SD below the expected range for their age) in 5/6 neurocognitive tasks. Children who scored low on the non-verbal reasoning task were more likely to have more parent- and teacher-rated behavioral problems, and children’s performance on the inhibitory control and cognitive flexibility tasks were associated with parent-rated behavioral problems. Children’s verbal reasoning scores were positively associated with both parent- and teacher-rated emotional problems. Children who were adopted later in childhood scored significantly lower in non-verbal reasoning. Although longitudinal studies are needed to clarify the nature of neurocognitive functioning as a marker for later mental health problems, our findings underscore the importance of using comprehensive assessments to better recognize adopted children’s difficulties and inform appropriate intervention initiatives

Geochemical characterization of shallow groundwater at the Cranfield aquifer and numerical simulation: Can pH and carbonate parameters be used to detect potential CO2 leakage at geological CO2 sequestration sites?

Bureau of Economic Geolog

Facial emotion recognition in adopted children

Children adopted from public care are more likely to experience emotional and behavioural problems. We investigated two aspects of emotion recognition that may be associated with these outcomes, including discrimination accuracy of emotions and response bias, in a mixed-method, multi-informant study of 4-to-8-year old children adopted from local authority care in the UK (N = 42). We compared adopted children’s emotion recognition performance to that of a comparison group of children living with their birth families, who were matched by age, sex, and teacher-rated total difficulties on the Strengths and Difficulties Questionnaire (SDQ, N = 42). We also examined relationships between adopted children’s emotion recognition skills and their pre-adoptive histories of early adversity (indexed by cumulative adverse childhood experiences), their parent- and teacher-rated emotional and behavioural problems, and their parents’ coded warmth during a Five Minute Speech Sample. Adopted children showed significantly worse facial emotion discrimination accuracy of sad and angry faces than non-adopted children. Adopted children’s discrimination accuracy of scared and neutral faces was negatively associated with parent-reported behavioural problems, and discrimination accuracy of angry and scared faces was associated with parent- and teacher-reported emotional problems. Contrary to expectations, children who experienced more recorded pre-adoptive early adversity were more accurate in identifying negative emotions. Warm adoptive parenting was associated with fewer behavioural problems, and a lower tendency for children to incorrectly identify faces as angry. Study limitations and implications for intervention strategies to support adopted children’s emotion recognition and psychological adjustment are discussed