Facial expression coding in children and adolescents with autism: Reduced adaptability but intact norm-based coding

Individuals with autism spectrum disorder (ASD) can have difficulty recognizing emotional expressions. Here we asked whether the underlying perceptual coding of expression is disrupted. Typical individuals code expression relative to a perceptual (average) norm that is continuously updated by experience. This adaptability of face coding mechanisms has been linked to performance on various face tasks. We used an adaptation aftereffect paradigm to characterize expression coding in children and adolescents with autism. We asked whether face expression coding is less adaptable in autism and whether there is any fundamental disruption of norm-based coding. If expression coding is norm-based, then the face aftereffects should increase with adaptor expression strength (distance from the average expression). We observed this pattern in both autistic and typically developing participants, suggesting that norm-based coding is fundamentally intact in autism. Critically, however, expression aftereffects were reduced in the autism group, indicating that expression-coding mechanisms are less readily tuned by experience. Reduced adaptability has also been reported for coding of face identity and gaze direction. Thus there appears to be a pervasive lack of adaptability in face-coding mechanisms in autism, which could contribute to face processing and broader social difficulties in the disorder

SARS-CoV-2-specific memory B cells can persist in the elderly who have lost detectable neutralising antibodies

Memory B cells (MBC) can provide a recall response able to supplement waning antibodies with an affinity-matured response better able to neutralise variant viruses. We studied a cohort of elderly care home residents and younger staff (median age 87yrs and 56yrs respectively) who had survived COVID-19 outbreaks with only mild/asymptomatic infection. The cohort was selected to enrich for a high proportion who had lost neutralising antibodies (nAb), to specifically investigate the reserve immunity from SARS-CoV-2-specific MBC in this setting. Class-switched spike and RBD-tetramer-binding MBC persisted five months post-mild/asymptomatic SARS-CoV-2 infection, irrespective of age. The majority of spike/RBD-specific MBC had a classical phenotype but activated memory B cells, that may indicate ongoing antigenic stimulation or inflammation, were expanded in the elderly. Spike/RBD-specific MBC remained detectable in the majority who had lost nAb, although at lower frequencies and with a reduced IgG/IgA isotype ratio. Functional spike/S1/RBD-specific recall was also detectable by ELISpot in some who had lost nAb, but was significantly impaired in the elderly. Our findings demonstrate a reserve of SARS-CoV-2-specific MBC persists beyond loss of nAb, but highlight the need for careful monitoring of functional defects in spike/RBD-specific B cell immunity in the elderly

Isolation of human intrahepatic leukocytes for phenotypic and functional characterization by flow cytometry

With the growing appreciation of tissue-resident immunity, studying tissue-specific immune cells contributing to both homeostasis and disease is imperative. Here, we provide a protocol for the isolation of human intrahepatic leukocytes (IHL) maximizing viability, purity, and yield. Our protocol is scalable by tissue weight, allowing for reproducible and efficient IHL liberation suitable for functional characterization, cell isolation, and profiling by flow (or mass) cytometry. Furthermore, we provide a "guide" to determine an expected IHL yield per gram of tissue processed. For complete details on the use and execution of this protocol, please refer to Stegmann et al. (2016), Pallett et al. (2017), Easom et al. (2018), Swadling et al. (2020), Pallett et al. (2020), and Zakeri et al. (2022)

A novel (1,4)-beta-linked glucoxylan is synthesized by members of the cellulose synthase-like F gene family in land plants

As a significant component of monocot cell walls, (1,3;1,4)-β-glucan has conclusively been shown to be synthesized by the cellulose synthase-like F6 protein. In this study, we investigated the synthetic activity of other members of the barley (Hordeum vulgare) CslF gene family using heterologous expression. As expected, the majority of the genes encode proteins that are capable of synthesizing detectable levels of (1,3;1,4)-β-glucan. However, overexpression of HvCslF3 and HvCslF10 genes resulted in the synthesis of a novel linear glucoxylan that consists of (1,4)-β-linked glucose and xylose residues. To demonstrate that this product was not an aberration of the heterologous system, the characteristic (1,4)-β-linkage between glucose and xylose was confirmed to be present in wild type barley tissues known to contain HvCslF3 and HvCslF10 transcripts. This polysaccharide linkage has also been reported in species of Ulva, a marine green alga, and has significant implications for defining the specificity of the cell wall content of many crop species. This finding supports previous observations that members of a single CSL family may not possess the same carbohydrate synthetic activity, with the CSLF family now associated with the formation of not only (1,3)- and (1,4)-β-glucosidic linkages, but also (1,4)-β-glucosidic and (1,4)-β-xylosidic linkages.Alan Little, Jelle Lahnstein, David W. Jeffery, Shi F. Khor, Julian G. Schwerdt, Neil J. Shirley, Michelle Hooi, Xiaohui Xing, Rachel A. Burton, and Vincent Bulon

Recognizing the same face in different contexts : Testing within-person face recognition in typical development and in autism

Unfamiliar face recognition follows a particularly protracted developmental trajectory and is more likely to be atypical in children with autism than those without autism. There is a paucity of research, however, examining the ability to recognize the same face across multiple naturally varying images. Here, we investigated within-person face recognition in children with and without autism. In Experiment 1, typically developing 6- and 7-year-olds, 8- and 9-year-olds, 10- and 11-year-olds, 12- to 14-year-olds, and adults were given 40 grayscale photographs of two distinct male identities (20 of each face taken at different ages, from different angles, and in different lighting conditions) and were asked to sort them by identity. Children mistook images of the same person as images of different people, subdividing each individual into many perceived identities. Younger children divided images into more perceived identities than adults and also made more misidentification errors (placing two different identities together in the same group) than older children and adults. In Experiment 2, we used the same procedure with 32 cognitively able children with autism. Autistic children reported a similar number of identities and made similar numbers of misidentification errors to a group of typical children of similar age and ability. Fine-grained analysis using matrices revealed marginal group differences in overall performance. We suggest that the immature performance in typical and autistic children could arise from problems extracting the perceptual commonalities from different images of the same person and building stable representations of facial identity

Targeting human Acyl-CoA:cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint

Determining divergent metabolic requirements of T cells, and the viruses and tumours they fail to combat, could provide new therapeutic checkpoints. Inhibition of acyl-CoA:cholesterol acyltransferase (ACAT) has direct anti-carcinogenic activity. Here, we show that ACAT inhibition has antiviral activity against hepatitis B (HBV), as well as boosting protective anti-HBV and anti-hepatocellular carcinoma (HCC) T cells. ACAT inhibition reduces CD8+ T cell neutral lipid droplets and promotes lipid microdomains, enhancing TCR signalling and TCR-independent bioenergetics. Dysfunctional HBV- and HCC-specific T cells are rescued by ACAT inhibitors directly ex vivo from human liver and tumour tissue respectively, including tissue-resident responses. ACAT inhibition enhances in vitro responsiveness of HBV-specific CD8+ T cells to PD-1 blockade and increases the functional avidity of TCR-gene-modified T cells. Finally, ACAT regulates HBV particle genesis in vitro, with inhibitors reducing both virions and subviral particles. Thus, ACAT inhibition provides a paradigm of a metabolic checkpoint able to constrain tumours and viruses but rescue exhausted T cells, rendering it an attractive therapeutic target for the functional cure of HBV and HBV-related HCC

Developmental changes in the critical information used for facial expression processing

Facial expression recognition skills are known to improve across childhood and adolescence, but the mechanisms driving the development of these important social abilities remain unclear. This study investigates directly whether there are qualitative differences in child and adult processing strategies for these emotional stimuli. With a novel adaptation of the Bubbles reverse-correlation paradigm (Gosselin & Schyns, 2001), we added noise to expressive face stimuli and presented sub-sets of randomly sampled information from each image at different locations and spatial frequency bands across experimental trials. Results from our large developmental sample: 71 young children (6 -9 years), 69 older children (10-13 years) and 54 adults, uniquely reveal flexible profiles of strategic information-use for categorisations of fear, sadness, happiness and anger at all ages. All three groups relied upon a distinct set of key facial features for each of these expressions, with fine-tuning of this diagnostic information (features and spatial frequency) observed across developmental time. Reported variability in the developmental trajectories for different emotional expressions is consistent with the notion of functional links between the refinement of information-use and processing ability

Resilience to obesity among socioeconomically disadvantaged women : the READI study

Objective: This cross-sectional study aimed to identify sociodemographic and behavioural characteristics of ‘overweight-resilient’ women, that is, women who were in a healthy body weight range, despite living in socioeconomically disadvantaged neighbourhoods that place them at increased risk of obesity. The study also aimed to test a comprehensive theoretically derived model of the associations between intrapersonal, social and environmental factors and obesity among this target group.Participants: A total of 3235 women aged 18–45 years from 80 urban and rural neighbourhoods throughout Victoria, Australia, participated in the Resilience for Eating and Activity Despite Inequality study.Measurements: Women reported height, weight, sociodemographic characteristics, leisure-time physical activity, dietary behaviours and a range of theoretically derived cognitive, social and neighbourhood environmental characteristics hypothesized to influence obesity risk. A theoretical model predicting body mass index (BMI) was tested using structural equation models.Results: Women classified as ‘resilient’ to obesity tended to be younger, born overseas, more highly educated, unmarried and to have higher or undisclosed household incomes. They engaged in more leisure-time physical activity and consumed less fast foods and soft drinks than overweight/obese women. Neighbourhood characteristics, social characteristics and cognitive characteristics all contributed to explaining variation in BMI in the hypothesized directions.Conclusions: These results demonstrate several characteristics of women appearing ‘resilient’ to obesity, despite their increased risk conferred by residing in socioeconomically disadvantaged neighbourhoods. Acknowledging the cross-sectional study design, the results advance theoretical frameworks aimed at investigating obesity risk by providing evidence in support of a comprehensive model of direct and indirect effects on obesity of neighbourhood, as well as social, cognitive and behavioural characteristics

Financial incentives to improve adherence to antipsychotic maintenance medication in non-adherent patients: a cluster randomised controlled trial

Background: Poor adherence to long-term antipsychotic injectable (LAI) medication in patients with psychotic disorders is associated with a range of negative outcomes. No psychosocial intervention has been found to be consistently effective in improving adherence. Objectives: To test whether or not offering financial incentives is effective and cost-effective in improving adherence and to explore patient and clinician experiences with such incentives. Design: A cluster randomised controlled trial with economic and nested qualitative evaluation. The intervention period lasted for 12 months with 24 months’ follow-up. The unit of randomisation was mental health teams in the community. Setting: Community teams in secondary mental health care. Participants: Patients with a diagnosis of schizophrenia, schizoaffective psychosis or bipolar illness, receiving ≤ 75% of their prescribed LAI medication. In total, 73 teams with 141 patients (intervention n = 78 and control n = 63) were included. Interventions: Participants in the intervention group received £15 for each LAI medication. Patients in the control group received treatment as usual. Main outcome measures: Primary outcome: adherence to LAI medication (the percentage of received out of those prescribed). Secondary outcomes: percentage of patients with at least 95% adherence; clinical global improvement; subjective quality of life; satisfaction with medication; hospitalisation; adverse events; and costs. Qualitative evaluation: semistructured interviews with patients in the intervention group and their clinicians. Results: Primary outcome: outcome data were available for 131 patients. Baseline adherence was 69% in the intervention group and 67% in the control group. During the intervention period, adherence was significantly higher in the intervention group than in the control group (85% vs. 71%) [adjusted mean difference 11.5%, 95% confidence interval (CI) 3.9% to 19.0%; p = 0.003]. Secondary outcome: patients in the intervention group showed statistically significant improvement in adherence of at least 95% (adjusted odds ratio 8.21, 95% CI 2.00 to 33.67; p = 0.003) and subjective quality of life (difference in means 0.71, 95% CI 0.26 to 1.15; p = 0.002). Follow-ups: after incentives stopped, adherence did not differ significantly between groups, neither during the first 6 months (adjusted difference in means –7.4%, 95% CI –17.0% to 2.1%; p = 0.175) nor during the period from month 7 to month 24 (difference in means –5.7%, 95% CI –13.1% to 1.7%; p = 0.130). Cost-effectiveness: the average costs of the financial incentives was £303. Overall costs per patient were somewhat higher in the intervention group, but the difference was not significant. Semistructured interviews: the majority of patients and clinicians reported positive experiences with the incentives beyond their monetary value. These included improvement in the therapeutic relationship. The majority of both patients and clinicians perceived no negative impact after the intervention was stopped after 1 year. Conclusions: Financial incentives are effective in improving adherence to LAI medication. Health-care costs (including costs of the financial incentive) are unlikely to be increased substantially by this intervention. Once the incentives stop, the advantage is not maintained. The experiences of both patients and clinicians are largely, but not exclusively, positive. Whether or not financial incentives are effective for patients with more favourable background, those on oral mediation or for shorter or longer time periods remains unknown. Trial registration: Current Controlled Trials ISRCTN77769281. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 70. See the NIHR Journals Library website for further project information