Single-cell analysis of human B cell maturation predicts how antibody class switching shapes selection dynamics.

Protective humoral memory forms in secondary lymphoid organs where B cells undergo affinity maturation and differentiation into memory or plasma cells. Here, we provide a comprehensive roadmap of human B cell maturation with single-cell transcriptomics matched with bulk and single-cell antibody repertoires to define gene expression, antibody repertoires, and clonal sharing of B cell states at single-cell resolution, including memory B cell heterogeneity that reflects diverse functional and signaling states. We reconstruct gene expression dynamics during B cell activation to reveal a pre-germinal center state primed to undergo class switch recombination and dissect how antibody class-dependent gene expression in germinal center and memory B cells is linked with a distinct transcriptional wiring with potential to influence their fate and function. Our analyses reveal the dynamic cellular states that shape human B cell-mediated immunity and highlight how antibody isotype may play a role during their antibody-based selection. This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Immunology on Science Immunology Vol. 6, Feb 2021, DOI: 10.1126/sciimmunol.abe6291

Two languages, two minds: flexible cognitive processing driven by language of operation.

People make sense of objects and events around them by classifying them into identifiable categories. The extent to which language affects this process has been the focus of a long-standing debate: Do different languages cause their speakers to behave differently? Here, we show that fluent German-English bilinguals categorize motion events according to the grammatical constraints of the language in which they operate. First, as predicted from cross-linguistic differences in motion encoding, bilingual participants functioning in a German testing context prefer to match events on the basis of motion completion to a greater extent than do bilingual participants in an English context. Second, when bilingual participants experience verbal interference in English, their categorization behavior is congruent with that predicted for German; when bilingual participants experience verbal interference in German, their categorization becomes congruent with that predicted for English. These findings show that language effects on cognition are context-bound and transient, revealing unprecedented levels of malleability in human cognition

Impaired implicit learning of syntactic structure in children with developmental language disorder:Evidence from syntactic priming

Background and aims Implicit learning mechanisms associated with detecting structural regularities have been proposed to underlie both the long-term acquisition of linguistic structure and a short-term tendency to repeat linguistic structure across sentences (structural priming) in typically developing children. Recent research has suggested that a deficit in such mechanisms may explain the inconsistent trajectory of language learning displayed by children with Developmental Learning Disorder. We used a structural priming paradigm to investigate whether a group of children with Developmental Learning Disorder showed impaired implicit learning of syntax (syntactic priming) following individual syntactic experiences, and the time course of any such effects. Methods Five- to six-year-old Italian-speaking children with Developmental Learning Disorder and typically developing age-matched and language-matched controls played a picture-description-matching game with an experimenter. The experimenter’s descriptions were systematically manipulated so that children were exposed to both active and passive structures, in a randomized order. We investigated whether children’s descriptions used the same abstract syntax (active or passive) as the experimenter had used on an immediately preceding turn (no-delay) or three turns earlier (delay). We further examined whether children’s syntactic production changed with increasing experience of passives within the experiment. Results Children with Developmental Learning Disorder’s syntactic production was influenced by the syntax of the experimenter’s descriptions in the same way as typically developing language-matched children, but showed a different pattern from typically developing age-matched children. Children with Developmental Learning Disorder were more likely to produce passive syntax immediately after hearing a passive sentence than an active sentence, but this tendency was smaller than in typically developing age-matched children. After two intervening sentences, children with Developmental Learning Disorder no longer showed a significant syntactic priming effect, whereas typically developing age-matched children did. None of the groups showed a significant effect of cumulative syntactic experience. Conclusions Children with Developmental Learning Disorder show a pattern of syntactic priming effects that is consistent with an impairment in implicit learning mechanisms that are associated with the detection and extraction of abstract structural regularities in linguistic input. Results suggest that this impairment involves reduced initial learning from each syntactic experience, rather than atypically rapid decay following intact initial learning. Implications Children with Developmental Learning Disorder may learn less from each linguistic experience than typically developing children, and so require more input to achieve the same learning outcome with respect to syntax. Structural priming is an effective technique for manipulating both input quality and quantity to determine precisely how Developmental Learning Disorder is related to language input, and to investigate how input tailored to take into account the cognitive profile of this population can be optimised in designing interventions

On the shopfloor: exploring the impact of teacher trade unions on school-based industrial relations

Teachers are highly unionised workers and their trade unions exert an important influence on the shaping and implementation of educational policy. Despite this importance there is relatively little analysis of the impact of teacher trade unions in educational management literature. Very little empirical research has sought to establish the impact of teacher unions at school level. In an era of devolved management and quasi-markets this omission is significant. New personnel issues continue to emerge at school level and this may well generate increased trade union activity at the workplace. This article explores the extent to which devolved management is drawing school-based union representation into a more prominent role. It argues that whilst there can be significant differences between individual schools, increased school autonomy is raising the profile of trade union activity in the workplace, and this needs to be better reflected in educational management research

Bereavement and palliative care: A public health perspective

In recent years there has been an increasing emphasis upon public health perspectives that place palliative care in the context of end-of-life services across whole populations. There is little corresponding public health interest in bereavement. Yet if we have to develop relevant, coherent, and comprehensive end-of-life care policies and practices, public health approaches to palliative care need to be accompanied by public health approaches to bereavement care. We argue here that palliative care services should match their commitment to providing a good death with a commitment to supporting good grief, and that this means investing their efforts principally in developing community capacity for bereavement care rather than seeking to deliver specialized bereavement services to relatives and friends of those who have received palliative care services

Elephants in pyjamas: testing the weak central coherence account of autism spectrum disorders using a syntactic disambiguation task

According to the weak central coherence (CC) account individuals with autism spectrum disorders (ASD) exhibit enhanced local processing and weak part-whole integration. CC was investigated in the verbal domain. Adolescents, recruited using a 2 (ASD status) by 2 (language impairment status) design, completed an aural forced choice comprehension task involving syntactically ambiguous sentences. Half the picture targets depicted the least plausible interpretation, resulting in longer RTs across groups. These were assumed to reflect local processing. There was no ASD by plausibility interaction and consequently little evidence for weak CC in the verbal domain when conceptualised as enhanced local processing. Furthermore, there was little evidence that the processing of syntactically ambiguous sentences differed as a function of ASD or language-impairment status

Introduction—Food Security and Food Waste Reduction: A Social Innovation Approach to Current Social, Environmental, and Political Concerns

This chapter presents the research rationale underpinning the book. It addresses the intertwining challenges of food security and surplus food management, discussing recent data and literature. It also presents how social innovation is conceptualized in the book as the theoretical framework to analyse partnerships between business and non-profit organisations in managing food surplus. The methodology of the research is also detailed, along with the book structure

Prediction of uncomplicated pregnancies in obese women: A prospective multicentre study

BACKGROUND: All obese pregnant women are considered at equal high risk with respect to complications in pregnancy and birth, and are commonly managed through resource-intensive care pathways. However, the identification of maternal characteristics associated with normal pregnancy outcomes could assist in the management of these pregnancies. The present study aims to identify the factors associated with uncomplicated pregnancy and birth in obese women, and to assess their predictive performance. METHODS: Data form obese women (BMI ≥ 30 kg/m 2 ) with singleton pregnancies included in the UPBEAT trial were used in this analysis. Multivariable logistic regression was used to identify sociodemographic, clinical and biochemical factors at 15 +0 to 18 +6 weeks' gestation associated with uncomplicated pregnancy and birth, defined as delivery of a term live-born infant without antenatal or labour complications. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC). Internal validation and calibration were also performed. Women were divided into fifths of risk and pregnancy outcomes were compared between groups. Sensitivity, specificity, and positive and negative predictive values were calculated using the upper fifth as the positive screening group. RESULTS: Amongst 1409 participants (BMI 36.4, SD 4.8 kg/m 2 ), the prevalence of uncomplicated pregnancy and birth was 36% (505/1409). Multiparity and increased plasma adiponectin, maternal age, systolic blood pressure and HbA1c were independently associated with uncomplicated pregnancy and birth. These factors achieved an AUROC of 0.72 (0.68-0.76) and the model was well calibrated. Prevalence of gestational diabetes, preeclampsia and other hypertensive disorders, preterm birth, and postpartum haemorrhage decreased whereas spontaneous vaginal delivery increased across the fifths of increasing predicted risk of uncomplicated pregnancy and birth. Sensitivity, specificity, and positive and negative predictive values were 38%, 89%, 63% and 74%, respectively. A simpler model including clinical factors only (no biomarkers) achieved an AUROC of 0.68 (0.65-0.71), with sensitivity, specificity, and positive and negative predictive values of 31%, 86%, 56% and 69%, respectively. CONCLUSION: Clinical factors and biomarkers can be used to help stratify pregnancy and delivery risk amongst obese pregnant women. Further studies are needed to explore alternative pathways of care for obese women demonstrating different risk profiles for uncomplicated pregnancy and birth