Evaluating the Effectiveness of a ‘Real‐World’ Shared Reading Intervention for Preschool Children and Their Families: A Randomised Controlled Trial

Background Shared reading interventions can impact positively on preschool children's language development and on their caregiver's attitudes/behaviours towards reading. However, a number of barriers may discourage families from engaging with these interventions, particularly families from lower socio‐economic status (SES) backgrounds. We investigated how families from such backgrounds responded to an intervention designed explicitly to overcome these barriers. Methods In a preregistered cluster randomised controlled trial, 85 lower SES families and their 3‐year‐old to 4‐year‐old children from 10 different preschools were randomly allocated to take part in The Reader's Shared Reading programme (intervention) or an existing ‘Story Time’ group at a library (control) once a week for 8 weeks. Three outcome measures were assessed at baseline and post intervention: (1) attendance, (2) enjoyment of the reading groups and (3) caregivers' knowledge of, attitudes and behaviours towards reading. A fourth − children's vocabulary – was assessed at baseline and 4 weeks post intervention. Results Families were significantly more likely to attend the intervention group and rated it more favourably, compared with the control group. However, there were no significant effects on caregivers' knowledge, attitudes and behaviours or on children's language. Conclusion The intervention was only successful in engaging families from disadvantaged backgrounds in shared reading. Implications for the use, duration and intensity of shared reading interventions are discussed

Children’s engagement and caregivers’ use of language-boosting strategies during shared book reading: A mixed methods approach

For shared book reading to be effective for language development, the adult and child need to be highly engaged. The current paper adopted a mixed-methods approach to investigate caregiver’s language-boosting behaviours and children’s engagement during shared book reading. The results revealed there were more instances of joint attention and caregiver’s use of prompts during moments of higher engagement. However, instances of most language-boosting behaviours were similar across episodes of higher and lower engagement. Qualitative analysis assessing the link between children’s engagement and caregiver’s use of speech acts, revealed that speech acts do seem to contribute to high engagement, in combination with other aspects of the interaction

Three-year-olds’ comprehension of contrastive and descriptive adjectives: Evidence for contrastive inference

Combining information from adjectives with the nouns they modify is essential for comprehension. Previous research suggests that preschoolers do not always integrate adjectives and nouns, and may instead over-rely on noun information when processing referring expressions (Fernald, Thorpe, & Marchman, 2010; Thorpe, Baumgartner, & Fernald, 2006). This disjointed processing has implications for pragmatics, apparently preventing under-fives from making contrastive inferences (Huang & Snedeker, 2013). Using a novel experimental design that allows preschoolers time to demonstrate their abilities in adjective-noun integration and in contrastive inference, two visual world experiments investigate how English-speaking three-year-olds (N = 73, Mage = 44 months) process size adjectives across syntactic (prenominal; postnominal) and pragmatic (descriptive; contrastive) contexts. We show that preschoolers are able to integrate adjectives and nouns to resolve reference accurately by the end of the referring expression, in a variety of pragmatic and syntactic contexts and in the presence of multiple distractors. We reveal for the first time that they can contrastively infer, given a slowed speed of presentation and visually salient size contrasts. Our findings provide evidence for a continuity in the development of pragmatic skills, which do not appear to be linked to children's language proficiency or speed of processing

Normalizing glycosphingolipids restores function in CD4+ T cells from lupus patients

Patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE) have multiple defects in lymphocyte signaling and function that contribute to disease pathogenesis. Such defects could be attributed to alterations in metabolic processes, including abnormal control of lipid biosynthesis pathways. Here, we reveal that CD4+ T cells from SLE patients displayed an altered profile of lipid raft–associated glycosphingolipids (GSLs) compared with that of healthy controls. In particular, lactosylceramide, globotriaosylceramide (Gb3), and monosialotetrahexosylganglioside (GM1) levels were markedly increased. Elevated GSLs in SLE patients were associated with increased expression of liver X receptor β (LXRβ), a nuclear receptor that controls cellular lipid metabolism and trafficking and influences acquired immune responses. Stimulation of CD4+ T cells isolated from healthy donors with synthetic and endogenous LXR agonists promoted GSL expression, which was blocked by an LXR antagonist. Increased GSL expression in CD4+ T cells was associated with intracellular accumulation and accelerated trafficking of GSL, reminiscent of cells from patients with glycolipid storage diseases. Inhibition of GSL biosynthesis in vitro with a clinically approved inhibitor (N-butyldeoxynojirimycin) normalized GSL metabolism, corrected CD4+ T cell signaling and functional defects, and decreased anti-dsDNA antibody production by autologous B cells in SLE patients. Our data demonstrate that lipid metabolism defects contribute to SLE pathogenesis and suggest that targeting GSL biosynthesis restores T cell function in SLE

Rationally designed immunogens enable immune focusing following SARS-CoV-2 spike imprinting

Eliciting antibodies to surface-exposed viral glycoproteins can generate protective responses that control and prevent future infections. Targeting conserved sites may reduce the likelihood of viral escape and limit the spread of related viruses with pandemic potential. Here we leverage rational immunogen design to focus humoral responses on conserved epitopes. Using glycan engineering and epitope scaffolding in boosting immunogens, we focus murine serum antibody responses to conserved receptor binding motif (RBM) and receptor binding domain (RBD) epitopes following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike imprinting. Although all engineered immunogens elicit a robust SARS-CoV-2-neutralizing serum response, RBM-focusing immunogens exhibit increased potency against related sarbecoviruses, SARS-CoV, WIV1-CoV, RaTG13-CoV, and SHC014-CoV; structural characterization of representative antibodies defines a conserved epitope. RBM-focused sera confer protection against SARS-CoV-2 challenge. Thus, RBM focusing is a promising strategy to elicit breadth across emerging sarbecoviruses without compromising SARS-CoV-2 protection. These engineering strategies are adaptable to other viral glycoproteins for targeting conserved epitopes

Reconstituted B cell receptor signaling reveals carbohydrate-dependent mode of activation

Activation of immune cells (but not B cells) with lectins is widely known. We used the structurally defined interaction between influenza hemagglutinin (HA) and its cell surface receptor sialic acid (SA) to identify a B cell receptor (BCR) activation modality that proceeded through non-cognate interactions with antigen. Using a new approach to reconstitute antigen-receptor interactions in a human reporter B cell line, we found that sequence-defined BCRs from the human germline repertoire could be triggered by both complementarity to influenza HA and a separate mode of signaling that relied on multivalent ligation of BCR sialyl-oligosaccharide. The latter suggested a new mechanism for priming naïve B cell responses and manifested as the induction of SA-dependent pan-activation by peripheral blood B cells. BCR crosslinking in the absence of complementarity is a superantigen effect induced by some microbial products to subvert production of antigen-specific immune responses. B cell superantigen activity through affinity for BCR carbohydrate is discussed

Cold Induces Micro- and Nano-Scale Reorganization of Lipid Raft Markers at Mounds of T-Cell Membrane Fluctuations

Whether and how cold causes changes in cell-membrane or lipid rafts remain poorly characterized. Using the NSOM/QD and confocal imaging systems, we found that cold caused microscale redistribution of lipid raft markers, GM1 for lipid and CD59 for protein, from the peripheral part of microdomains to the central part on Jurkat T cells, and that cold also induced the nanoscale size-enlargement (1/3- to 2/3-fold) of the nanoclusters of lipid raft markers and even the colocalization of GM1 and CD59 nanoclusters. These findings indicate cold-induced lateral rearrangement/coalescence of raft-related membrane heterogeneity. The cold-induced re-distribution of lipid raft markers under a nearly-natural condition provide clues for their alternations, and help to propose a model in which raft lipids associate themselves or interact with protein components to generate functional membrane heterogeneity in response to stimulus. The data also underscore the possible cold-induced artifacts in early-described cold-related experiments and the detergent-resistance-based analyses of lipid rafts at 4°C, and provide a biophysical explanation for recently-reported cold-induced activation of signaling pathways in T cells. Importantly, our fluorescence-topographic NSOM imaging demonstrated that GM1/CD59 raft markers distributed and re-distributed at mounds but not depressions of T-cell membrane fluctuations. Such mound-top distribution of lipid raft markers or lipid rafts provides spatial advantage for lipid rafts or contact molecules interacting readily with neighboring cells or free molecules