Reflections from the Classroom: Towards a Radical Pedagogy for Early Years

This article comprises some critical reflections on the teaching of a second year undergraduate module called Children’s Cultural Worlds in which students are required to engage with original studies which are then used to stimulate self-reflection and engagement with wider issues relating to our understanding of children’s place in the social world. It will be argued that when individual memories are shared, it is possible to identify continuities and discontinuities in childhood experiences as well as the intersections between childhood and other social divisions such as gender, class and ethnicity. The requirement that students recall and reflect on their childhood memories and share them with others is a way of students learning through their own experiences, reflecting on their views and values. Furthermore, as it will be shown, it opens up spaces for alternative values and viewpoints to emerge about how we might ‘regulate’ early childhood because ‘When we tell stories and process them, using reflective dialogues, we create the possibility of change in ourselves and others’.</jats:p

Unconventional human CD61 pairing with CD103 promotes TCR signaling and antigen-specific T cell cytotoxicity

Cancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer treatments. In the past decade, CD103+ T cells have been associated with better clinical prognosis in patients with cancer. However, the specific immune mechanisms contributing toward CD103-mediated protective immunity remain unclear. Here, we show an unexpected and transient CD61 expression, which is paired with CD103 at the synaptic microclusters of T cells. CD61 colocalization with the T cell antigen receptor further modulates downstream T cell antigen receptor signaling, improving antitumor cytotoxicity and promoting physiological control of tumor growth. Clinically, the presence of CD61+ tumor-infiltrating T lymphocytes is associated with improved clinical outcomes, mediated through enhanced effector functions and phenotype with limited evidence of cellular exhaustion. In conclusion, this study identified an unconventional and transient CD61 expression and pairing with CD103 on human immune cells, which potentiates a new target for immune-based cellular therapies

Sex differences in the neuroanatomy of alcohol dependence: hippocampus and amygdala subregions in a sample of 966 people from the ENIGMA Addiction Working Group

Males and females with alcohol dependence have distinct mental health and cognitive problems. Animal models of addiction postulate that the underlying neurobiological mechanisms are partially distinct, but there is little evidence of sex differences in humans with alcohol dependence as most neuroimaging studies have been conducted in males. We examined hippocampal and amygdala subregions in a large sample of 966 people from the ENIGMA Addiction Working Group. This comprised 643 people with alcohol dependence (225 females), and a comparison group of 323 people without alcohol dependence (98 females). Males with alcohol dependence had smaller volumes of the total amygdala and its basolateral nucleus than male controls, that exacerbated with alcohol dose. Alcohol dependence was also associated with smaller volumes of the hippocampus and its CA1 and subiculum subfield volumes in both males and females. In summary, hippocampal and amygdalar subregions may be sensitive to both shared and distinct mechanisms in alcohol-dependent males and females

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities